Phototherapy and Photochemotherapy (PUVA) for Skin Conditions
Number: 0205
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses phototherapy and photochemotherapy (PUVA) for skin conditions.
-
Medical Necessity
Aetna considers the following interventions medically necessary:
-
Psoralens and ultraviolet A light (PUVA) treatments for the following conditions after conventional therapies have failed:
- Alopecia areata
- Chronic palmoplantar pustulosis
- Cutaneous T-cell lymphoma (mycosis fungoides)
- Cutaneous manifestations of graft versus host disease
- Eosinophilic folliculitis and other pruritic eruptions of HIV infection
- Granuloma annulare
- Grover's disease (transient and persistent acantholytic dermatosis)
- Lymphomatoid papulosis
- Morphea (circumscribed scleroderma) and localized skin lesions associated with scleroderma
- Necrobiosis lipoidica
- Photodermatoses
- Pityriasis lichenoides
- Polymorphous light eruption
- Severe lichen planus
- Severe parapsoriasis
- Severe refractory atopic dermatitis/eczema
- Severe refractory pruritus of polycythemia vera
- Severe urticaria pigmentosa (cutaneous mastocytosis)
- Severely disabling psoriasis (i.e., psoriasis involving 10 % or more of the body, or severe psoriasis involving the hands, feet, or scalp)
- Vitiligo;
Note: Generally 2 to 3 PUVA treatments per week for up to 23 weeks are considered medically necessary for psoriasis. After 23 weeks, the medically necessary frequency of PUVA therapy is 1 treatment every 1 to 3 weeks with the majority of persons treated once every 3 weeks for an indefinite period. If the psoriasis fails to improve after 2 months of PUVA therapy, continued treatment is generally not considered medically necessary due to lack of efficacy.
-
Phototherapy with UVA for the following indications:
- Acne
- Eczema (atopic dermatitis)
- Eosinophilic folliculitis and other pruritic eruptions of HIV infection
- Lichen planus
- Morphea (circumscribed scleroderma)
- Parapsoriasis
- Photodermatoses
- Pityriasis lichenoides
- Pityriasis rosea
- Prurigo nodularis
- Psoriasis
- Scleredema that is functionally limiting or symptomatic;
-
Narrow-band UVB phototherapy for the following indications:
- Atopic dermatitis (atopic eczema)
- Chronic urticaria
- Cutaneous mastocytosis (after conventional therapies have failed)
- Cutaneous T-cell lymphoma
- Early-stage mycosis fungoides/Sézary syndrome
- Granuloma annulare
- Kyrle disease (perforating dermatosis) that is refractory to topical or intralesional therapy
- Lichen planus
- Morphea (circumscribed scleroderma)
- Photodermatoses (e.g., actinic dermatitis and solar urticaria)
- Pityriasis lichenoides chronica
- Polymorphous light eruption
- Psoriasis
- Prurigo nodularis that is refractory to topical or intralesional corticosteroids
- Uremic pruritus that is refractory to emollients, topical analgesics and oral antihistamines or gabapentin
- Vitiligo (see CPB 0422 - Vitiligo);
- UVB with the addition of topical coal tar (also known as the Goeckerman regimen) for persons with severe psoriasis (defined as psoriasis that affects more than 10 % of body surface area);
- Home phototherapy (UVB) treatment:
- As DME for persons with severe psoriasis with a history of frequent flares who are unable to attend on-site therapy or those needing to initiate therapy immediately to suppress psoriasis flares
- For persons with atopic dermatitis (eczema) who are unable to attend on-site therapy;
-
Home ultraviolet light booths or ultraviolet lamps, as well as replacement bulbs sold by prescription only, for persons eligible for home UVB phototherapy.
-
-
Experimental, Investigational, or Unproven
The following interventions are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established:
-
PUVA treatment for all indications other than those listed as medically necessary above, including:
- Acne
- Eosinophilic cellulitis (Wells syndrome)
- Keratosis follicularis (Darier disease or Darier-White disease)
- Lichen amyloidosis
- Lichen myxedematosus
- Melasma
- Necrobiotic xanthogranuloma
- Necrobiosis lipoidica
- To increase skin tolerance to sunlight;
-
The use of UVA for all indications other than those listed as medically necessary above, including:
- Infectious keratitis
- Lymphomatoid papulosis
- Uremic pruritus;
-
Narrow-band UVB phototherapy for all indications other than those listed as medically necessary above, including:
- Alopecia mucinosa
- Chemical dermatitis/contact dermatitis
- Cholestasis of pregnancy
- COVID-19
- Darier disease
- Dermatographic urticaria (also known as dermographism and dermatographism)
- Disseminated superficial actinic porokeratosis (DSAP)
- Drug-related hypersensitivity reaction
- Erythema annulare centrifugum
- Erythematous hyper-pigmented macules/papules
- Graft-versus-host disease
- Grover's disease (transient and persistent acantholytic dermatosis)
- Hailey-Hailey disease
- Hidradenitis suppurativa
- Hypersensitive rash
- Lichen amyloidosis
- Lichen sclerosus
- Lichen simplex chronicus
- Lichenoid dermatitis
- Lymphomatoid papulosis
- Papular mucinosis
- Papular urticaria
- Progressive macular hypomelanosis
- Pruritus
- Scleroderma
- Skin hypo-pigmentation from scarring
- Superficial mixed-cell dermatitis;
- Home phototherapy (UVB) for the treatment of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), and indications other than psoriasis and atopic dermatitis (eczema);
- Home PUVA treatment because of insufficient evidence of its safety;
- UVB with the addition of topical coal tar for all indications other than psoriasis (e.g., pemphigoid, pruritis);
- Use of petrolatum or emollients before ultraviolet radiation, as the clinical benefits this practice have not been evaluated in well controlled trials.
-
-
Policy Limitations and Exclusions
Aetna considers tanning beds for home UVB phototherapy not medically necessary. Unlike tanning beds, home UVB devices are designed solely for the medical treatment of skin diseases and emit a different wavelength of ultraviolet light than tanning beds. In addition, tanning beds do not meet Aetna's definition of covered durable medical equipment in that they are of use in the absence of illness or injury.
-
Related Policies
- CPB 0422 - Vitiligo - for narrow-band UVB phototherapy for vitiligo
- CPB 0577 - Laser Treatment for Psoriasis and Other Selected Skin Conditions - for excimer laser treatment of psoriasis
- CPB 0656 - Photodynamic Therapy for Acne
Code | Code Description |
---|---|
PUVA: |
|
CPT codes covered if selection criteria are met: |
|
96912 | Photochemotherapy; psoralens and ultraviolet A (PUVA) |
96913 | Photochemotherapy (Goeckerman and/or PUVA) for severe photoresponsive dermatoses requiring at least 4-8 hours of care under direct supervision of the physician (includes applications of medication and dressings) |
ICD-10 codes covered if selection criteria are met: |
|
B20 | Human immunodeficiency virus [HIV] disease |
C84.00 - C84.09 C84.A0 - C84.A9 |
Mycosis fungoides and cutaneous T-cell lymphoma |
C86.6 | Primary cutaneous CD30-positive T-cell proliferations |
D45 | Polycythemia vera |
D89.810 - D89.813 | Graft-versus-host disease |
L11.1 | Transient acantholytic dermatosis [Grover] |
L20.0 - L20.82 L20.84 - L20.9 |
Atopic dermatitis [severe refractory] |
L29.0 - L29.9 | Puritis [refractory uremic pruritus] |
L40.0 - L40.9 | Psoriasis [severe disabling, involving 10% or more of body or severe psoriasis involving the hands, feet or scalp] |
L41.0 - L41.9 | Parapsoriasis [severe] |
L43.0 - L43.9, L66.1 | Lichen planus [severe] |
L56.4 | Polymorphous light eruption |
L56.8 | Other specified acute skin changes due to ultraviolet radiation |
L63.0 - L63.9 | Alopecia areata |
L80 | Vitiligo |
L92.0 | Granuloma annulare |
L94.0 | Localized scleroderma [morphea] |
Q82.2 | Mastocytosis [Urticaria pigmentosa] [severe] |
T86.09 | Other complications of bone marrow transplant [skin conditions] |
ICD-10 codes not covered for indications listed in CPB (not all-inclusive): |
|
D76.3 | Other histiocytosis syndromes. Reticulohistiocytoma (giant-cell); Sinus histiocytosis with massive lymphadenopathy; Xanthogranuloma |
E85.4 [L99 also required] |
Organ-limited amyloidosis [lichen amyloidosis] |
L70.0 - L70.9 | Acne |
L81.1 | Chloasma [melasma] |
L98.3 | Eosinophilic cellulitis [Wells] |
L98.5 | Mucinosis of the skin [lichen myxedematosus] |
Q82.8 | Other specified congenital malformations of skin [Darier-White] |
ICD-10 codes contraindicated for this CPB: |
|
C43.0 - C43.9 | Malignant melanoma of skin |
C44.00 - C44.99 | Other and unspecified malignant neoplasm of skin |
O00.00 - O9a.53 | Pregnancy, childbirth and the puerperium |
L58.0 - L58.9 [W88.0xx+ - W88.8xx+ also required] |
Radiodermatitis [history of ionizing radiation exposure] |
L59.0 - L59.9 [T66.xxxS also required] |
Other disorders of skin and subcutaneous tissue related to radiation [late effect of ionizing radiation exposure] |
T37.8x1+ - T37.8x4+ | Poisoning by arsenical anti-infectives [history of arsenic exposure] |
T57.0x1+ - T57.0x4+ | Toxic effect of arsenic and its compounds [history of arsenic exposure] |
T66.xxx+ | Radiation sickness, unspecified [history of ionizing radiation exposure] |
Z34.00 - Z34.93 | Encounter for supervision of normal pregnancy |
Z85.820 | Personal history of malignant melanoma of skin |
Z85.828 | Personal history of other malignant neoplasm of skin |
UVA/UVB: |
|
CPT codes covered if selection criteria are met: |
|
96900 | Actinotherapy (ultraviolet light)[Narrow-band UVB][not covered for severe urticaria pigmentosa (cutaneous mastocytosis)] |
96913 | Photochemotherapy (Goeckerman and/or PUVA) for severe photoresponsive dermatoses requiring at least four to eight hrs of care under direct supervision of the physician (includes applications of medication and dressings) |
ICD-10 codes covered if selection criteria are met: |
|
B20 | Human immunodeficiency virus [HIV] disease |
C84.00 - C84.09 C84.A0 - C84.A9 |
Mycosis fungoides and cutaneous T-cell lymphoma |
L20.0 - L20.82 L20.84 - L20.9 |
Atopic dermatitis [severe refractory] |
L24.9 | Irritant contact dermatitis, unspecified cause |
L25.9 | Unspecified contact dermatitis, unspecified cause |
L30.0 | Nummular dermatitis |
L30.1 | Dyshidrosis [pompholyx] |
L30.2 | Cutaneous autosensitization |
L30.8 - L30.9 | Other specified and unspecified dermatitis |
L40.0 - L40.9 | Psoriasis [severe disabling, involving 10% or more of body or severe psoriasis involving the hands, feet or scalp] |
L41.0 - L41.9 | Parapsoriasis [severe] |
L42 | Pityriasis rosea |
L43.0 - L43.9, L66.1 | Lichen planus |
L56.4 | Polymorphous light eruption |
L63.0 - L63.9 | Alopecia areata |
L70.0 - L70.9 | Acne |
L80 | Vitiligo |
L92.0 | Granuloma annulare |
L94.0 | Localized scleroderma [morphea] [only UVA is covered for morphea - not UVB] |
M34.81 - M34.89 | Other forms of systemic sclerosis [scleroderma] |
T86.09 | Other complications of bone marrow transplant [skin conditions] |
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive): |
|
H16.001 - H16.9 | Keratitis [infectious] |
L12.0, L12.8 - L12.9 | Pemphigoid |
L12.1 | Cicatricial pemphigoid [benign mucous membrane pemphigoid] |
L12.2 | Chronic bullous disease of childhood [Juvenile dermatitis herpetiformis] |
L29.0 - L29.9 | Puritis |
L73.2 | Hidradenitis suppurativa |
M34.0 - M34.2 | Systemic sclerosis [scleroderma] |
P83.0 | Sclerema neonatorum |
Q82.2 | Xeroderma pigmentosum |
Q82.8 | Other specified congenital malformations of skin |
Home phototherapy (UVB treatment)(not covered for home PUVA): |
|
HCPCS codes covered if selection criteria are met: |
|
A4633 | Replacement bulb/lamp for ultraviolet light therapy system, each |
E0691 | Ultraviolet light therapy system panel, includes bulbs/lamps, timer and eye protection; treatment area 2 sq feet or less |
E0692 | Ultraviolet light therapy system panel, includes bulbs/lamps, timer and eye protection; 4 ft panel |
E0693 | Ultraviolet light therapy system panel, includes bulbs/lamps, timer and eye protection; 6 ft panel |
E0694 | Ultraviolet multidirectional light therapy system in 6 ft cabinet, includes bulbs/lamps, timer and eye protection |
ICD-10 codes covered if selection criteria are met: |
|
L20.0-L20.82 L20.84-L20.9 |
Atopic dermatitis [atopic eczema] |
L40.0 - L40.9 | Psoriasis [severe/ with frequent flares/ needing to initiate therapy immediately/ unable to attend on-site therapy] |
ICD-10 codes not covered for indications listed in the CPB: |
|
C84.00 – C84.09 | Mycosis fungoides |
C84.10 – C84.19 | Sezary disease |
C84.A0 – C84.A9 | Cutaneous T-cell lymphoma |
Narrow-band UVB: |
|
CPT codes covered if selection criteria are met: |
|
96900 | Actinotherapy (ultraviolet light)[Narrow-band UVB][not covered for severe urticaria pigmentosa (cutaneous mastocytosis)] |
ICD-10 codes covered if selection criteria are met: |
|
C84.00 - C84.09 C84.A0 - C84.A9 |
Mycosis fungoides and cutaneous T-cell lymphoma |
C84.10 – C84.19 | Sezary disease |
D47.01 | Cutaneous mastocytosis |
L20.0 - L20.82 L20.84 - L20.9 |
Atopic dermatitis [atopic eczema] |
L28.1 | Prurigo nodularis |
L29.8 | Other pruritus [uremic pruritus] |
L40.8 | Other psoriasis |
L41.1 | Pityriasis lichenoides chronica |
L43.0 - L43.9 | Lichen planus |
L50.6 - L50.8 | Contact and other urticaria [papular] [chronic urticaria if first-line therapies (e.g. systemic corticosteroids and methotrexate) have failed] |
L56.3 | Solar urticaria |
L56.4 | Polymorphous light eruption |
L56.8 - L56.9 | Other specified and unspecified acute skin changes due to ultraviolet radiation |
L57.8 | Other skin changes due to chronic exposure to nonionizing radiation [actinic dermatitis] |
L80 | Vitiligo |
L87.0 | Keratosis follicularis et parafollicularis in cutem penetrans [Kyrle disease] |
L92.0 | Granuloma annulare |
L94.0 | Localized scleroderma [morphea] |
L94.1 | Linear scleroderma |
L94.3 | Sclerodactyly |
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive): |
|
C86.6 | Primary cutaneous CD30-positive T-cell proliferations |
D72.12 | Drug rash with eosinophilia and systemic symptoms syndrome [hypersensitive rash] |
D89.810 - D89.813 | Graft-versus-host disease |
E85.4 | Organ-limited amyloidosis [lichen amyloidosis] |
L11.1 | Transient acantholytic dermatosis [Grover] |
L23.0 - L24.7 | Allergic and Irritant contact dermatitis [superficial mixed-cell dermatitis] |
L27.0 | Generalized skin eruption due to drugs and medicaments taken internally [erythematous hyper-pigmented macules/papules] |
L28.0 | Lichen simplex chronicus [lichenoid dermatitis] |
L29.0 - L29.9 | Pruritis |
L50.3 | Dermatographic urticaria |
L53.1 | Erythema annulare centrifugum |
L56.5 | Disseminated superficial actinic porokeratosis (DSAP) |
L65.2 | Alopecia mucinosa |
L73.2 | Hidradenitis suppurative |
L81.4 | Other melanin hyperpigmentation [erythematous hyper-pigmented macules/papules] |
L81.7 | Pigmented purpuric dermatosis [erythematous hyper-pigmented macules/papules] |
L81.8 | Other specified disorders of pigmentation [melasma][ progressive macular hypomelanosis] [erythematous hyper-pigmented macules/papules] |
L81.9 | Disorder of pigmentation, unspecified [skin hypo-pigmentation from scarring] |
L90.0 | Lichen sclerosus et atrophicus |
L94.0 | Localized scleroderma [morphea] |
L98.5 | Mucinosis of the skin |
M34.0 - M34.9 | Systemic sclerosis [scleroderma] |
O26.611 - O26.619 | Liver and biliary tract disorders in pregnancy [cholestasis of pregnancy] |
Q81.0 - Q81.9 | Epidermolysis bullosa |
Q82.8 | Other specified congenital malformations of skin [Darier-White] |
R21 | Rash and other nonspecific skin eruption [hypersensitive rash] |
T88.7XXA - T88.7XXS | Unspecified adverse effect of drug or medicament [drug-related hypersensitivity reaction] |
U07.1 | Covid 19 |
UVB with the addition of topical coal tar (also known as the Goeckerman regimen): |
|
CPT codes covered if selection criteria are met: |
|
96910 | Photochemotherapy; tar and ultraviolet B (Goeckerman treatment) or petrolatum and ultraviolet B |
ICD-10 codes covered if selection criteria are met: |
|
L40.0 - L40.9 | Psoriasis [severe, that affects more than 10% of body surface area] |
Background
- history of arsenic exposure; or
- history of ionizing radiation exposure; or
- history or presence of melanoma or other skin cancer; or
- pregnancy.
Khan and colleagues (2011) presented the first 3 cases of Acanthamoeba keratitis (AK), unresponsive to medical treatment, that were successfully treated with a novel adjunctive therapy using UVA and riboflavin (B2). Two patients with confirmed AK and 1 patient with presumptive AK, which were all refractive to multi-drug conventional therapy were included in this study. Two treatment sessions involving topical application of 0.1% B2 solution to the ocular surface combined with 30 mins of UVA irradiation focused on the corneal ulcer were carried out. Main outcome measures were clinical examination by slit lamp, confocal microscopy, and histopathology, when available. All patients in these series showed a rapid reduction in their symptoms and decreased ulcer size after the first treatment session. The progress of the clinical improvement began to slow after 1 to 3 weeks of the first application and was then renewed after the second application. All ancillary signs of inflammation mostly resolved after the second treatment session. The ulcers in all patients continued to decrease and were closed within 3 to 7 weeks of the first application. Two patients developed dense central corneal scars, and penetrating keratoplasty was performed for visual rehabilitation. Histopathological examination of the excised tissue revealed no Acanthamoeba organisms. The remaining patient had no symptoms or signs of infection, both clinically and by confocal microscopy, and was left with a semi-transparent eccentric scar that did not affect visual acuity. The authors concluded that adjunctive use of UVA and B2 therapy seems to be a possible alternative for selected cases of medication-resistant AK. Moreover, they noted that further research is needed and currently underway to examine how best to use photochemical therapy for the treatment of infectious keratitis.
Lowe (1992) stated that home UV phototherapy is extremely popular with many psoriasis patients. However, it is essential that they understand the need for regular skin examination by the dermatologist. Patients with psoriasis are not trained nor are many non-dermatologist physicians to recognize the early features of many skin cancers, and continued home UV therapy in the presence of such skin cancers is clearly unwise for the safety of that patient. The use of UVA tanning salon treatments in the therapy of psoriasis is usually unsuccessful and is extremely unwise with concomitant psoralen and drug therapy. This is to be discouraged, and the patient should always be treated with PUVA in the dermatologist's office with carefully monitored UVA machines and staff trained in the administration of PUVA phototherapy.
In an open-label, randomized controlled trial, van Coevorden et al (2004) examined if oral PUVA with a portable tanning unit at home is as effective as hospital-administered bath PUVA in patients with chronic hand eczema. A total of 158 patients with moderate-to-severe chronic hand eczema (more than 1 year in duration) were included in this study. The primary outcome was clinical assessment by a hand eczema score (evaluation of desquamation, erythema, vesiculation, infiltration, fissures, itch, and pain, each on a 4-point scale) after 10 weeks of treatment. The secondary outcome was hand eczema score at 8 weeks of follow-up, after completion of treatment. The tertiary outcome was travel cost and time off work. Both groups showed a comparable and substantial decrease in hand eczema score (meaningful clinical improvement). This decrease was maintained during the follow-up period. Patients treated with oral PUVA at home had lower travel costs and less time off work. The authors concluded that oral PUVA at home has a clinically relevant efficacy, similar to that of hospital-administered bath PUVA. This effect was maintained during an 8-week follow-up period. It resulted in lower travel costs and less time off work. These promising results need to be validated by more research.
Dermatographic urticaria (also known as dermographism and dermatographism) is a skin disorder observed in 4 to 5% of the population and is one of the most common types of urticaria, in which the skin becomes raised and inflamed when stroked, scratched, rubbed, and sometimes even slapped. Dermatographic urticaria can be treated by anti-histamines, which may need to be given as a combination of H1 antagonists, or possibly with an H2-receptor antagonist such as cimetidine. Therapies may also include immunosuppressive agents and steroids. There is a lack of evidence regarding the clinical value of narrow-band UVB phototherapy in the treatment of this condition.
Kreutz et al (2012) noted that depletion of host Langerhans cells (LCs) prevents cutaneous graft-versus-host disease (GVHD) in mice. These researchers analyzed whether UVB irradiation is tolerated during the course of human allogeneic hematopoietic cell transplantation and whether depletion of LCs by broadband UVB could improve GvHD outcome. A total of 17 patients received 6 whole-body UVB irradiations with 75% of the individually determined minimal erythemal dose after conditioning with a reduced intensity protocol. Langerhans cells, dermal dendritic cells (DCs), and macrophages were analyzed before and after UVB irradiation by immunohistochemical analysis. Circulating blood cells and serum factors were analyzed in parallel. In striking contrast to previous data, this irradiation protocol was well-tolerated in all patients. Treatment with UVB decreased the number of LCs and also affected dermal DCs. Patients treated with UVB also had significantly higher 25-hydroxyvitamin D3 serum levels and higher numbers of circulating CD4+ FoxP3+ regulatory T cells. Strikingly, 9 out of 9 patients with complete LC depletion (less than 1 LC per field) developed only grade I GVHD or no GVHD up to day 100. The authors concluded that these results strongly suggest that prophylactic UVB irradiation post-transplant is safe and should be further explored as a clinical strategy to prevent acute (skin) GVHD.
Duarte et al (2010) noted that progressive macular hypomelanosis (PMH) is a common dermatosis; its cause is unknown and proposed treatments have had little effect. These researchers examined epidemiological aspects of PMH in patients referred to a phototherapy clinic between 1997 and 2008 and evaluated therapeutic response to PUVA (psoralen + UVA) photochemotherapy or narrow-band ultraviolet B (NB-UVB) phototherapy. A total of 84 patients with PMH were evaluated. After 16 phototherapy sessions, therapeutic response was classified as: unchanged, slightly improved (less than 50% of re-pigmentation), moderately improved (50 to 79% of re-pigmentation), much improved (80 to 99%) or cured (100%). After a minimum of 3 months, patients whose response was classified as cured or much improved were contacted by telephone to evaluate the persistence of the therapeutic response. Most of the patients were women (79%) and white (85%). Age at onset of PMH ranged from 13 to 36 years. PUVA was prescribed for 27 patients and NB-UVB phototherapy for 57. No significant difference was found between the outcomes obtained with PUVA and those obtained with NB-UVB phototherapy (Fisher's exact test; p < 0.05). The majority of patients (81%) had 50% or more re-pigmentation, with 65% being classified as cured or much improved. Nevertheless, there was a recurrence of the lesions in 72% of patients. The authors concluded that the fact that no patients were over 40 years of age suggested that PMH is a self-limiting disease. Both PUVA and NB-UVB are effective therapeutic options; however, they do not prevent recurrence of the disease. The main drawback of this study was its uncontrolled nature and small sample size.
Montero et al (2011) stated that PMH is an acquired disorder of skin pigmentation, which is mostly under-diagnosed. It is characterized by nummular hypo-pigmented lesions appearing on the trunk in young persons. Several treatment options are available, although topical clindamycin and benzoyl peroxide have been used traditionally. However, good results have recently been achieved using NB-UVB phototherapy. These researchers presented the case of a 13-year old girl with hypo-pigmented lesions on the trunk and limbs that had progressed over 1 year and that were diagnosed as PMH. The patient was initially treated with topical clindamycin and benzoyl peroxide. However, little improvement was seen and treatment was then started with NB-UVB phototherapy. After 25 sessions, with a total cumulative dose of 18 J/cm(2), the patient showed almost total re-pigmentation of the lesions. The treatment of PMH is often difficult, and very little is currently known about the treatment response in this disorder, as most reports have very small series of patients with a short disease progression time. The authors concluded that NB-UVB phototherapy has been shown to be effective, as seen in this patient, although in many cases, there is recurrence after the cessation of treatment.
Kim et al (2012) examined the clinical features of PMH in Koreans and determined the therapeutic efficacy of NB-UVB therapy in the management of PMH. These investigators performed an uncontrolled prospective study designed to evaluate the usefulness of NB-UVB therapy in PMH. A total of 23 patients with PMH were enrolled in the study. Of these, 17 patients underwent treatment with NB-UVB therapy once- or twice-weekly and were eligible for analysis. The remaining 6 patients were lost to follow-up before completion of the treatment. Re-pigmentation was evaluated by 2 dermatologists using photographic documentation. Narrow band-UVB therapy was used successfully in 9 of 16 patients (56.2%), who showed more than 90% re-pigmentation. They found that 13 of 16 patients (81.3%) experienced at least 50% re-pigmentation. The re-pigmented sites showed an excellent color match. No signs of recurrence have been detected in 11 of these 16 patients (68.7%) up to the present time (13.2 +/- 8.2 months of follow-up). The authors concluded that the findings of this study suggested that NB-UVB therapy is an effective and safe method for use in the treatment of PMH. Drawbacks of this study included a small number of subjects examined, and it was an uncontrolled and non-double-blind study.
Berg et al (1994) carried out a study in 22 patients with polymorphous light eruption (PMLE) who were prophylactically treated with UVA with and without trimethylpsoralen; 12 of the patients were treated during 2 consecutive springs with placebo during one spring and psoralens during the other. Eighteen of the patients improved after the therapy, but there was no clear-cut difference between the 2 regimens. As many as 12 patients got light eruptions during the treatment, but all but 1 continued with the therapy. The authors concluded that the findings of this study indicated that UVA alone is as good prophylactic therapy for PMLE as PUVA with trimethylpsoralen. However, because of the high incidence of provoked eruptions during therapy, the treatment may be difficult to handle for the patients themselves, at least during the initial treatment.
- mild,
- moderate-to-severe,
- severe, and
- therapy-resistant.
These classifications are useful for determining appropriate prophylactic measurements. No specific laboratory tests were available for the diagnosis of PLE, therefore, a clinician must rely on the clinical appearance of the disorder (e.g., clinical symptoms, the location of the lesions, the relationship of the occurrence of the lesions with sun exposure and the time course of the lesions) as well as a patient's medical history in order to make a diagnosis. Basic preventative management of PLE consists of adequate sun protection comprising avoidance of sun exposure, the use of textile sun protection and the application of broadband sunscreens with high UVA protection potential. Other supportive measurements have to be managed individually and are dependent on the patient's medical history and the severity of the disease. Topical anti-oxidants, systemic immunomodulation, photo(chemo)therapy and systemic immunosuppression may be required in some cases of PLE. Topical anti-oxidants represent a new treatment approach for moderate-to-severe PLE and are an effective and well-tolerated option for this patient population. Severe PLE also requires photo(chemo)therapy. Phototherapy can be in the form of 311-nm UVB or UVA1 irradiation. In cases where 311-nm UVB or UVA1 are ineffective, psoralen plus UVA (PUVA) bath therapy may be used. However, PUVA bath therapy must be used with caution because it is associated with acute and long-term adverse effects. In rare exceptions we would consider using oral PUVA therapy. However, in our outpatient department, quality of life of most patients is improved with the treatment regimens that are recommended for patients with moderate-to-severe PLE, without the need for photo(chemo)therapy.
An UpToDate review on “Polymorphous light eruption” (Elmets, 2013) states that that PUVA plus psoralens is considered second-line therapy for PMLE.
First-line therapies Includes the following:
- Sun protection - Sun protection is first-line therapy for patients with PMLE and includes sun avoidance, sun protective clothing, and sunscreens. Sunscreens should be broad spectrum, with both UVA and UVB protection. A sunscreen with an SPF (sun protection factor) of at least 30 should be regularly applied. Products containing photostabilized avobenzone or ecamsule (Mexoryl SX) offer improved protection against UVA, and have been effective in preventing PMLE eruptions. Sunscreens that contain the non-micronized form of zinc oxide or titanium dioxide also offer photoprotection that extends throughout the UV and into the visible spectrum. Examples of broad spectrum sunscreens containing photostabilized avobenzone or ecamsule, or zinc oxide and titanium oxide are provided.
- Topical corticosteroids - No randomized trials have evaluated the efficacy of topical corticosteroids for PMLE. Clinical experience suggests that potent topical corticosteroids (groups one to three) may be used for symptomatic relief, and may be sufficient pharmacologic therapy for mild cases. Facial lesions should be treated with lower potency topical corticosteroids (groups six to seven).
Second-line therapies include the following:
- Phototherapy - Prophylactic phototherapy with low dose PUVA (psoralens plus UVA) or UVB in early spring to induce tolerance to sun exposure may be an option for patients who are expected to develop significant symptoms during the spring or summer. Treatments are usually given 2 to 3 times per week over 5 to 6 weeks.
- PUVA therapy is superior to broadband UVB. In one randomized trial, treatment was successful in 92% of patients treated with PUVA, compared with 62% of patients treated with broadband UVB. In contrast, a small randomized trial showed narrowband UVB to be as effective as PUVA. Because narrowband UVB is easier to administer, it is often preferred to PUVA therapy for patients with PMLE. Narrowband UVB phototherapy can be administered 3 times per week, starting with a dose equivalent to 50 to 70% of the MED. The dose is increased during subsequent treatments as tolerated by the patient.
Treatment-induced exacerbations may occur early in the course of phototherapy. If these occur, potent topical corticosteroids (groups one to three) or a short course of oral glucocorticoid therapy (e.g., prednisone 1 mg per kg for 7 to 10 days) may be required.
Samson et al (2003) reviewed the evidence regarding NB-UVB for the treatment for vitiligo, pruritus, and inflammatory dermatoses. This was a retrospective review of the treatment outcomes of 117 consecutive patients with vitiligo, pruritus, and other inflammatory dermatoses, excluding those with psoriasis and cutaneous T-cell lymphoma (CTCL), who were treated with NB-UVB between 1998 and 2001 at the authors’ institution. Approximately 80% of all patients showed improvement in their condition. Narrow-band UVB phototherapy was well-tolerated, with no serious adverse effects. In patients with vitiligo, 6.4% had an abnormal thyroid-stimulating hormone level and 6.5% had anemia. The authors concluded that NB-UVB may be considered as a viable therapeutic option in the treatment of vitiligo, pruritus, and other inflammatory dermatoses. Moreover, they stated that long-term adverse effects and cost-benefit analysis of NB-UVB therapy compared to other treatment modalities remain to be determined.
Gambichler et al (2005) provided an update on clinical experiences in NB-UVB of non-psoriatic skin conditions, and established its current position within the spectrum of competing photo(chemo)therapeutic options. The computerized bibliographic database PubMed, without time limits, and other sources were screened for clinical trials on NB-UVB. Included were research articles of randomized controlled trials (RCTs), open prospective studies, and retrospective observations on NB-UVB in skin disorders other than psoriasis. A total of 28 articles met eligibility criteria including 6 RCTs, 16 open prospective studies, and 6 retrospective observations. Narrow-band UVB is effective in patients with chronic atopic dermatitis (AD) (n = 719) and generalized vitiligo (n = 305) and appears to have some advantages over competing photo(chemo)therapeutic regimens. Narrow-band UVB also seems to be effective in patients with PMLE (n = 25), early stages of CTCL (n = 108), chronic urticaria (n = 88), lichen planus (n = 15), pruritus associated with polycythemia vera (n = 10), seborrheic dermatitis (n = 18), actinic prurigo (n = 6), and acquired perforating dermatosis (n = 5). The quality of evidence determined for the afore-mentioned diagnoses ranged from high to moderate to very low. The authors concluded that the best currently available data on NB-UVB in non-psoriatic conditions exist for AD and generalized vitiligo. In view of its efficacy, benefit/risk profile, and costs, NB-UVB may be considered the first-line photo(chemo)therapeutic option for moderately severe AD and widespread vitiligo. In the treatment of most other non-psoriatic conditions, NB-UVB appears to be effective, but current data allow no definitive conclusions as to whether NB-UVB should be preferred to competing photo(chemo)therapeutic options such as PUVA regimens. Because NB-UVB may have a wider indication spectrum, including AD, vitiligo, and early-stage CTCL, and appears to be equally effective or even more effective than broad-band UVB (BB-UVB), a switch from BB-UVB to NB-UVB seems to be justified. This study had a small number of patients with PMLE (n = 25).
Pugashetti and colleagues (2010) noted that BB-UVB phototherapy has demonstrated effectiveness in the treatment of cutaneous disorders including psoriasis, AD, uremic pruritus and idiopathic pruritus. In the last decade, there has been a rapidly escalating process of replacing BB-UVB phototherapy units with NB-UVB equipment, as studies have demonstrated that NB-UVB (ranging from 311 mm to 312 nm) is more effective in the treatment of psoriasis. Nevertheless, it is important to recognize the efficacy of BB-UVB phototherapy in the treatment of uremic pruritus, idiopathic pruritus, eosinophilic folliculitis and other inflammatory pruritic conditions. Furthermore, as high-lighted in this report, there was a small but significant proportion of psoriasis and AD patients who do not tolerate NB-UVB but demonstrated an excellent clinical response to BB-UVB. It is critical for dermatologists to recognize the role of BB-UVB as a complement to NB-UVB phototherapy for patients who cannot tolerate or experience an inadequate therapeutic response from NB-UVB. This study did not mention PMLE as an indication of BB-UVB or NB-UVB.
Walker and Jacobe (2011) stated that dermatologists are presented with a diversity of therapeutic modalities for the treatment of inflammatory, sclerosing, and neoplastic conditions, but with the development of various new irradiation devices that utilize specific parts of the electromagnetic spectrum, phototherapy has become a more viable, accessible, and effective option in the treatment of these conditions. The UV range (10 to 400 nm) is further sub-divided into UVA and UVB, each of which has been particularly useful in a number of skin conditions. The most commonly used forms of UV irradiation are UVA1, PUVA, and NB-UVB. Each of these modalities differ in their mechanism of action, indications, and side effect profiles, and it is important that clinicians be familiar with these differences. Today, phototherapy is a valuable option in the treatment of many non-psoriatic conditions including AD, sclerosing skin conditions such as morphea, vitiligo, and mycosis fungoides. Due to its relative safety, phototherapy may be used in most populations, including children and pregnant women. However, contraindications and side effects are known and should be considered before patients begin a phototherapeutic regimen. Again, this study did not mention PMLE as an indication of BB-UVB or NB-UVB.
Veith et al (2011) noted that phototherapy is used for the medical care of cutaneous conditions that do not respond to topical or systemic medical agents, and for conditions that require broad exposure to UV as a stabilizing agent for disease. Numerous wavelengths and delivery devices of UV light are used in childhood. This article was a brief overview of the medical usage of phototherapy in childhood. In the neonatal nursery blue light (459 to 460 nm) is used to reduce bilirubin levels and prevent kernicterus. While PUVA has been demonstrated to be effective in a variety of pediatric skin conditions, NB-UVB therapy (311 nm) has largely replaced PUVA as initial choice in full-body phototherapy for children. The latter is easier to deliver, with less resultant erythema than systemic PUVA, which requires strict use of 24-hour protective eyewear. Narrowband-UVB is therefore preferred for stabilization and clearance of a variety of inflammatory and autoimmune conditions especially AD, psoriasis and vitiligo. Conditions with lymphocytic infiltration, including mycosis fungoides, alopecia areata and pityriasis lichenoides can improve with NB-UVB as well. Alternatively, localized delivery of NB-UVB can be performed using the Excimer laser (308 nm), which has been described for the therapy of vitiligo and alopecia areata in childhood. Some diseases with dermal infiltration including morphea and mastocytosis may do better with PUVA or UVA1. Delivery of psoralens can also be performed topically for said conditions and in the setting of alopecia areata, thereby limiting UVA exposure, while retaining efficacy. Phototherapy can be a helpful adjunct in pediatric skin disease, but is limited by compliance issues. Parents can act as partners in the safe and effective delivery of phototherapy by standing outside the booth or inside with the child to ensure lack of movement and to aid in maintenance of eyewear. Choice of type of phototherapy and close monitoring, with parental partnership, is the key to successful treatment. Again, this study did not mention PMLE as an indication of BB-UVB or NB-UVB.
Also, an UpToDate review on “Polymorphous light eruption” (Elmets, 2013) does not mention the use of photochemotherapy/Goeckerman treatment as therapeutic options. The review provides several “Summary and Recommendations”:
- UVA is the most common inciting spectrum of light, but UVB and visible light may also provoke PMLE in some patients
- Primary treatment for PMLE includes sun avoidance, sun-protective clothing, and sunscreen. Broad spectrum sunscreens with an SPF of at least 30 should be regularly used
- For patients with active lesions, we suggest treatment with potent topical corticosteroids (groups one to three). An alternative in patients with infrequent exacerbations, particularly those who require rapid improvement, is a short course of systemic glucocorticoids
- For patients who develop frequent exacerbations during the spring and summer, we suggest prophylactic phototherapy in early spring
- Juvenile spring eruption is a variant of PMLE that is manifested by erythematous papules or bullae typically on ears of children or adolescents after sun exposure. Symptoms are self-limited and resolve within several weeks
Note: Regarding UVB in the treatment of prurigo nodularis, Ferrandiz et al (1997) reported that an excellent response was obtained after an average of 32 UVB courses.
Note: Delrosso et al (2008) reported that an aggressive bath PUVA treatment is not substantially more effective in clearing chronic plaque-type psoriasis than a milder therapeutic approach.
Tan et al (2010) reviewed the efficacy and tolerability of NB-UVB phototherapy in children at a tertiary center in New Zealand, and determined if there were any factors that differentiated responders from non-responders. These researchers performed a prospective analysis of children (less than 16 years old) who had undergone phototherapy over a 15-year period. A total of 116 children received phototherapy with a total of 144 courses. Mean age was 11.0 years with the majority being European and having skin phototype II. Atopic dermatitis was the most common indication for treatment followed by psoriasis, pityriasis lichenoides, nodular prurigo, morphea, vitiligo, urticaria pigmentosa and erythropoietic porphyria. Treatment was effective in the majority of children (72%). Most received only 1 course. For responders, the mean number of treatments was 32.4. The mean dose per treatment to achieve clearance was 886 mJ/cm(2) and the mean maximum treatment dose per treatment was 1,328 mJ/cm(2). All children tolerated treatment well with 36% developing brief, minimally symptomatic, erythema. Only 2 children experienced exacerbations of their underlying dermatoses. The authors concluded that the findings of this study showed that phototherapy is an effective and well-tolerated treatment modality in children.
Weibel (2012) stated that localized scleroderma or morphea is a sclerosing connective tissue disease of the skin, which may affect underlying tissues such as subcutis, muscle and bone. Many patients show extra-cutaneous symptoms and anti-nuclear antibodies, however, secondary transformation into systemic sclerosis does not occur. Localized scleroderma usually begins in childhood with a wide variation in its clinical spectrum. The linear variant is the most common subtype in children, associated with a progressive course and increased risk of complications. The disease may progress over years and result in severe functional and cosmetic disability. The etiology of localized scleroderma remains unknown. A genetic background is suspected, while triggers such as trauma, vaccinations and infections may lead to secondary immunologic phenomena. Localized scleroderma often remains unrecognized for a long time, resulting in substantial delay in treatment. The combination of systemic corticosteroids and methotrexate has been established as first-line therapy for progressive (usually linear) disease, whereas phototherapy (UVA-1 or NB-UVB) is suitable for adolescents with superficial circumscribed subtypes.
Newland and Marshman (2012) stated that post-irradiation morphea is a rare but under-recognized complication of radiotherapy treatment for breast cancer. Management of this condition is difficult, and many cases are recalcitrant to therapy. A 43-year old woman with breast cancer received radiotherapy following a mastectomy and partial axillary lymph node dissection, shortly after which she developed a hot, tender, erythematous and indurated plaque at the mastectomy site. Subsequently the skin became retracted, depressed and hyper-pigmented. The clinical features, along with histological findings, were consistent with post-irradiation morphea. Treatment with NB-UVB and acitretin 10 mg daily was commenced 5 years following radiotherapy. After 2 months of therapy the patient reported significant improvement in tenderness and range of left arm movement. Objectively the plaque was less indurated and softer to palpation. The authors proposed that this treatment regimen is an option in the management of post-irradiation morphea.
Spalek et al (2015) noted that radiation-induced morphea (RIM) is a rare and under-recognized skin complication of radiotherapy. It is commonly wrongly diagnosed as other dermatological conditions or malignancy because of similar clinical characteristics. This literature review analyzed 66 cases that have been reported in the literature since 1989. The clinical appearance often includes pain and disfiguration of affected area, which may influence the patient's quality of life. There is no clear connection between the radiotherapy dose, the fractionation scheme, the use of a boost, age, the presence of other dermatological conditions or other connective tissue diseases and the occurrence of RIM. Its pathogenesis is still unclear, but several theories are proposed to explain this phenomenon. The available data suggested that the abnormally high secretion of some cytokines (interleukin 4, interleukin 5, transforming growth factor) induced by radiation causes an extensive fibrosis after an activation of fibroblasts. Histological confirmation is crucial in distinguishing RIM from similar-looking diseases, such as chronic radiation dermatitis, cancer recurrence, radiation, recall dermatitis, new carcinoma or cellulitis. There is no clear treatment regimen for this condition. Clinical outcome after therapy is often unsatisfactory. The commonly used methods and agents include: topical and systemic steroids, calcineurin inhibitors, systemic immunosuppressants including methotrexate, tacrolimus, heparin, hyaluronidase, phototherapy (UVA, UVA1, UVB, PUVA), systemic antibiotics, imiquimod, mycophenolate mofetil, photopheresis. The differential diagnosis is challenging and requires a multi-disciplinary approach to avoid misdiagnosis and to plan appropriate treatment.
Mizuno et al (2014) noted that Hailey-Hailey disease (HHD) is a rare autosomal dominant disorder characterized by development of recurrent blisters, erosions, and crustations in the intertriginous areas. The treatment of HHD is often challenging, and various methods have been tried. These investigators reported the case of a 45-year old woman with a generalized form of HHD that was dramatically improved and well controlled by NB-UVB phototherapy. This preliminary finding needs to be validated by well-designed studies.
An UpToDate review on “Hailey-Hailey disease (benign familial pemphigus)” (Morrell, 2014) does not mention phototherapy/NB-UVB as a therapeutic option.
Treister et al (2015) evaluated the safety and effectiveness of intra-oral NB-UVB phototherapy in the management of oral chronic GVHD (cGVHD). Patients with oral cGVHD were treated using a custom NB-UVB unit for a course of 24 phototherapy sessions. Treatments were initiated at 50 mJ/cm2 and increased by 10% at each visit unless toxicity was noted. Toxicity and response were assessed weekly. A total of 11 patients received a median of 22 (range of 4 to 39) NB-UVB treatments; 5 patients completed 24 treatments and elected to receive a median of 7 additional treatments. Median symptom scores (0 to 10) for sensitivity, pain, and dryness at baseline/end of therapy were 7.5, 3, 1, and 3, 1, 2, respectively. Taking into account all patient-reported outcomes, 7/11 patients had improvement and 2/11 worsened. At least partial improvement was reported in 8/11 patients with none reporting worsening. Over-treatment occurred in 10/11 patients with all graded mild or moderate and resolving in 1 to 2 days. The authors concluded that intra-oral NB-UVB may be effective for management of refractory oral cGVHD. They stated that further optimization of treatment parameters, as well as minimal erythema dose testing, and inclusion of a control arm are needed in the consideration of future studies.
The American Academy of Dermatology (AAD) state that "topical agents form the mainstay of treatment in psoriasis and all other treatment modalities are often used with concomitant topical therapy. Emollients increase the transmission of UV radiation by altering the optical properties of psoriatic skin lesions and improving therapeutic efficacy. Application of a thin layer of emollient such as petrolatum before UV exposure is traditionally used. However, there are no randomized controlled studies to prove the benefit of concomitant use of emollients with UVB. It is important to pay attention to the application of sunscreens or salicylic acid containing preparations that may interfere with the penetration of UV radiation. UV blocking properties may be used to cover uninvolved skin with preparations such as zinc oxide to prevent unnecessary exposure and adverse effect" (AAD, 2018).
Petrolatum and other emollients have been used prior to phototherapy (National Eczema Association, 2023), based upon the theory is that emollients like mineral oil or petroleum jelly increases the transmission of UV radiation to reduce the required dose of phototherapy and speed disease resolution (Mohammad, et al., 2017; Morison, 2005). However, there are no controlled trials proving that this has any effect on clinical outcomes. An UpToDate chapter on UVB phototherapy (Honigsman, et al., 2023) explains: “Emollients (eg, petrolatum, salicylic acid ointments) increase the transmission of UV radiation by altering the optical properties of the stratum corneum. Application of a thin layer of emollient such as petrolatum before UVB exposure is used in some institutions. However, the benefits of emollients before UVB exposure have not been evaluated in randomized trials.”
UVB for the Treatment of Photodermatoses
Collins and Ferguson (1995) reported that 20 patients with photodermatoses [actinic prurigo (n = 6), hydroa vacciniforme (n = 4), idiopathic solar urticaria (n = 1), amiodarone-induced photosensitivity (n = 1) and a range of cutaneous porphyrias (n = 8)] were treated with a “hardening” course of narrow-band ultraviolet (UV) B (TL-01) phototherapy in springtime. The response to phototherapy was monitored subjectively, by interviewing patients after the summer, and objectively by monochromator photo-testing, before and after phototherapy. Fifteen patients reported that treatment was worthwhile. Monochromator photo-testing after phototherapy revealed a 4-fold increase in the minimal erythema dose (MED) in those with abnormal photosensitivity to ultraviolet A wavebands. Adverse effects included erythema (n = 7), pruritus (n = 5) and provocation of the eruption (n = 4). The authors concluded that they now routinely consider narrow-band UVB phototherapy for problem photodermatoses.
Gupta et al (2000) stated that hydroa vacciniforme (HV) is a rare, sporadic, idiopathic photodermatosis characterized by vesicles and crust formation after sunlight exposure. The lesions typically heal with vacciniform scarring. These researchers identified and reviewed the clinical features and follow-up data of Scottish patients with HV and reported on the prevalence of this condition. They noted that this was the largest recent study of HV patients from a single center. In this retrospective study, patients with HV were identified by means of the diagnostic database from the Photobiology Unit, Dundee. Patients were contacted and details of clinical features, duration of disease, results of investigations, and treatment were recorded. At review, disease progress was assessed. Between 1973 and 1997, a total of 17 patients (9 males and 8 females) with a diagnosis of HV were investigated. Data from 15 patients showed a mean age at onset of 7.9 years (range of 1 to 16 years), with females (mean of 6.7 years; range of 2 to 12 years) having an earlier onset than males (mean of 8.7 years; range of 1 to 16 years). A bi-modal age distribution was also identified with onsets between the ages of 1 and 7 years and 12 and 16 years. At review, spontaneous clearing had occurred in 9 patients (60%) with mean duration of disease being 9 years (range of 4 to 17 years). Males had longer disease duration (mean of 11 years; range of 5 to 17 years) than females (mean of 5 years; range of 4 to 7 years). Eight patients (53%) were sensitive in the UVA wave-band on monochromator photo-testing, and 6 (40%) experienced papulo-vesicular lesions on repetitive broad-spectrum UVA irradiation. All patients received broad-spectrum sunscreens with variable results. Of the 5 patients treated with narrow-band UVB (TL-01) phototherapy, 3 reported beneficial results with an increase in tolerance to sunlight exposure and associated reduction in disease severity. The authors concluded that the estimated prevalence of HV was at least 0.34 cases per 100,000 with an approximately equal sex ratio. Males had a later onset and longer duration of disease than females. Photo-testing showed abnormal responses in the UVA wavebands in 53% of cases, whereas 60% of patients treated with prophylactic TL-01 phototherapy found it beneficial.
Dummer et al (2003) stated that polymorphous light eruption (PLE), a type of idiopathic photodermatoses, is an eruption induced by ultraviolet (UV) radiation (UVR). These researchers evaluated the clinical aspects, diagnostic criteria of PLE in a major Swiss referral center. A total of 25 patients (22 women and 3 men) with PLE were tested with a standardized protocol for the assessment of photodermatoses. Papular and papular-vesicular eruptions were the most common clinical presentations; 6 of 25 patients had a reduced MED for UVA and 8 of 25 patients had a reduced MED for UVB. Photo-provocation was positive in 11 of 20 patients for UVA and 7 of 20 patients for UVB. Photo-hardening with narrow-band UVB was successful in 8 of 10 patients. Combined UVA/UVB therapy had a satisfactory effect in 10 of 15 patients. Narrow-band UVB therapy was still successful after ineffective UVA/UVB therapy. The authors concluded that MED was of no value for the diagnosis of PLE. The typical lesions were reproduced by UVA and UVB photo-provocation. These investigators recommended photo-hardening with narrow-band UVB (311 nm).
Fesq et al (2003) stated that optimal management of patients with PLE, the most frequent photodermatosis, requires knowledge of the individual clinical course of the disease and pathogenic factors. As PLE often causes problems during leisure-time activities and holidays, resulting in a substantial loss of quality of life, prophylaxis is the most important therapeutic approach. Management of PLE must, therefore, focus on basic preventative measures and additional therapeutic approaches, depending on the clinical condition. PLE can be classified into 4 severity groups (mild, moderate-to-severe, severe and therapy-resistant), which are useful for determining appropriate prophylactic measurements. No specific laboratory tests are available for the diagnosis of PLE, therefore, a clinician must rely on the clinical appearance of the disorder (e.g., clinical symptoms, the location of the lesions, the relationship of the occurrence of the lesions with sun exposure and the time course of the lesions) as well as a patient's medical history in order to make a diagnosis. Basic preventative management of PLE consists of adequate sun protection comprising avoidance of sun exposure, the use of textile sun protection and the application of broad-band sunscreens with high UVA protection potential. Other supportive measurements have to be managed individually and are dependent on the patient's medical history and the severity of the disease. Topical antioxidants, systemic immunomodulation, photo(chemo)therapy and systemic immunosuppression may be required in some cases of PLE. Topical antioxidants represent a new treatment approach for moderate-to-severe PLE and are an effective and well-tolerated option for this patient population. Severe PLE also requires photo(chemo)therapy. Phototherapy can be in the form of 311 nm UVB (narrow-band UVB) or UVA1 irradiation. In cases where 311 nm UVB or UVA1 are ineffective, psoralen plus UVA (PUVA) bath therapy may be used. However, PUVA bath therapy must be used with caution because it is associated with acute and long-term adverse effects. In rare exceptions the authors would consider using oral PUVA therapy. However, in their outpatient department, quality of life of most patients is improved with the treatment regimens that are recommended for patients with moderate-to-severe PLE, without the need for photo(chemo)therapy.
Khaled et al (2011) stated that chronic actinic dermatitis (CAD) is a debilitating photodermatosis with characteristic clinical, histological and photo-biological features (reduced MED). Its management involves various therapeutic approaches, among them there is phototherapy. Efficacy of psoralen ultraviolet therapy (PUVA therapy) was previously demonstrated but there are no current data on the use of narrowband UVB therapy (NB-UVB) in CAD. NB-UVB has already been proven to be effective and safe in several other photodermatoses. These researchers reported the findings of 2 dark-skinned patients (skin type IV and V) with CAD, successfully treated with an incremental regimen of NB-UVB phototherapy coupled to a 3 month-course of systemic steroids (1 mg/Kg/day). The authors concluded that their protocol of NB-UVB with steroids appeared to be effective for the management of CAD with a good short-term safety profile.
An UpToDate review on “Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment” (Elmets, 2015) states that “Actinic prurigo -- Phototherapy with narrowband UVB or psoralen plus ultraviolet A (PUVA) is a therapeutic option in patients with persistent symptoms …. Chronic actinic dermatitis -- Low-dose PUVA or narrowband UVB, initially given with oral glucocorticoids to decrease treatment-induced flares, has been effective in small case series …. Solar urticaria -- Pharmacologic therapy or photodesensitization with low-dose PUVA or narrowband UVB initially given with oral glucocorticoids is usually required for management …. ”.
An UpToDate chapter on management of granuloma annulare (Brodell, 2023) states that, for patients who prefer to avoid systemic therapy, narrowband ultraviolet B phototherapy is an acceptable alternative. The author states that small, retrospective studies suggest benefit of narrow band UVB phototherapy.
European S1 guidelines on the management of lichen planus (Ioannides, et al., 2020) recommend either broadband or narrowband UVB as second line treatments for cutaneous manifestations of lichen planus. Narrowband or broadband UVB is also recommended as a third line treatment for mucosal lichen planus.
NCCN guidelines on primary cutaneous lymphomas (NCCN, 2023) recommends phototherapy for primary cutaneous CD30+ T-cell lymphoproliferative disorders. The guidelines state that narrowband UVB is generally preferred over PUVA.
PUVA for Eosinophilic Cellulitis (Wells Syndrome)
Raßler et al (2016) noted that eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and bullae, and granulomatous eosinophilic infiltrates in the dermis. Usually the disease has a benign course with spontaneous remission within a few weeks. Nevertheless, recurrences are quite frequent and may occur for several years. These investigators reviewed the therapeutic options for Wells syndrome in a systematic manner, which was based on a search on Medline, Embase and Cochrane Central Register for English and German articles from 1970 to 2015. Advices on the treatment of Wells syndrome were limited predominately to case reports or to small case-series studies. There were no RCTs, and control groups were missing. A variety of therapeutic options for Wells syndrome were reported including anti-histamines, anti-malarial medications, azathioprine, colchicine, cyclosporine, dapsone, doxycycline, griseofulvin, interferon alpha and gamma, minocycline, oral tacrolimus/topical tacrolimus, PUVA therapy, sulfasalazine, tumor necrosis factor (TNF)-alpha inhibitors, as well as topical and systemic corticosteroids. As well-designed RCTs are missing, no guidelines for the treatment of this disease can be given. The authors noted that due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview was to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. The authors concluded that due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions.
PUVA for Necrobiotic Xanthogranuloma
Miguel and colleagues (2017) stated that necrobiotic xanthogranuloma (NXG) is an uncommon non-Langerhans cell histiocytosis involving skin and extracutaneous tissues. The lesions are usually asymptomatic and commonly appear in the peri-orbital area. Paraproteinemia is closely associated with NXG and its pathogenesis remains unclear. NXG prognosis is poor with several treatments showing variable results. Treatment of monoclonal gammopathy with alkylating agents does not necessarily influence the activity of the skin disease and vice versa. These researchers summarized all reported treatments of necrobiotic xanthogranuloma of the skin, with or without underlying malignant condition and based on articles from the PubMed database using the query “necrobiotic xanthogranuloma treatment”, both in English and German, about “human” subjects and published between 1980 and 2014, documenting adequate treatment for NXG. Mainly individual case reports, small case series and retrospective studies were found. Therapeutic options include azathioprine, chlorambucil, cladribine, cyclophosphamide, extracorporeal photopheresis, fludarabine, high-dose intravenous immunoglobulin (IVIG), hydroxychloroquine, infliximab, interferon alpha, laser therapy, melphalan, methotrexate, plasmapheresis, PUVA, radiotherapy, rituximab, surgery, thalidomide, as well as topical and systemic corticosteroids. The authors stated that RCTs and studies on long-term outcomes after treatment were not found and are needed to focus on in the future.
Phototherapy for Scleredema
An UpToDate chapter on scleredema (Kreuter, 2017) states that, for patients with functionally limiting or symptomatic scleredema that is not expected to resolve spontaneously, initial treatment with phototherapy is suggested. This is a grade 2C recommendation based upon a retrospective study and case reports. The authors stated that, when available, they prefer to use UVA1 phototherapy. Improvement in scleredema has also been reported with PUVA and narrowband UVB phototherapy.
Kalfa and associates (2015) noted that scleredema is a rare connective tissue disorder of unknown pathogenesis; and 3 types of scleredema have been described, based on its association with post-infection, monoclonal gammopathy and diabetes mellitus. These investigators reported a case of scleredema in which the diagnosis didn't get specified. The patient was followed regularly for 13 years and did not respond to various combinations of immunosuppressants and PUVA therapy. The authors concluded that treatment of scleredema is quite difficult and of limited success. At present, there is no proved treatment for this disease.
Narrow-Band UVB for the Treatment of Chronic Urticaria
- 12 patients subjected to PUVA and
- 12 subjected to NB-UVB.
They were compared according to the urticaria Total Severity Score (TSS) before and after treatment, cumulative dose, and adverse events (AEs). There was a statistically significant decrease in urticaria TSS in both the NB-UVB- and PUVA-treated groups after than before treatment (p < 0.05), with no significant difference between both groups regarding the percentage of improved patients and the mean decrease of urticaria TSS (p > 0.05). Gastro-intestinal upset was reported at a significantly higher percentage in the PUVA-treated group than in the NB-UVB-treated group. The authors concluded that both NB-UVB and PUVA showed comparable effectiveness in the treatment of CU with minimal reversible AEs.
In a randomized, prospective, observer-blinded comparative study, Bishnoi and colleagues (2017) compared the effectiveness of PUVA and NB-UVB in steroid-dependent anti-histamine-refractory CU. A total of 50 patients with steroid-dependent CRU (6 months of spontaneous urticaria with no response after 3 consecutive months of anti-histamines and steroid dependence) were administered either PUVA (group A) or NB-UVB (group B) for 90 days, with a post-treatment follow-up of 90 days. Treatment effectiveness was assessed using the average urticaria activity score 7 (aUAS7) and outcome scoring scale (OSS) every 2 weeks. The mean values of aUAS7 progressively decreased from 4.9 ± 0.8 and 5.0 ± 0.7 at baseline to 1.9 ± 0.7 and 1.4 ± 0.7 in groups A and B, respectively, by day 90. This further decreased to 1.5 ± 0.8 and 1.4 ± 1.0 at day 180 in both groups. The values of OSS progressively increased from baseline (1.6 ± 0.5 in group A and 1.3 ± 0.5 in group B) to 3.9 ± 0.3 and 4.0 ± 0.3 in groups A and B, respectively, by day 90, and 3.9 ± 0.5 and 4.0 ± 0.6 by day 180. NB-UVB fared statistically better than PUVA at different time-points; AEs encountered were minimal and did not warrant treatment discontinuation. The authors concluded that phototherapy, especially NB-UVB, is a safe and effective therapeutic modality for steroid-dependent CU and should be tried prior to 3rd-line treatment options (e.g., cyclosporine and omalizumab).
Narrow-Band UVB for the Treatment of Alopecia Mucinosa
An Medscape review on “Alopecia Mucinosa” (Gerstner, 2017) stated that “No uniformly effective therapy exists for alopecia mucinosa, although several treatments are routinely used. Treatments include topical, intralesional, and systemic corticosteroids. In addition, topical and systemic psoralen plus ultraviolet A light (PUVA) therapy, topical nitrogen mustard, and radiation therapy have demonstrated some success. Isolated cases document the beneficial responses of dapsone, indomethacin, and interferons. Because of the variable course of the disease and the likelihood of spontaneous resolution, therapeutic efficacy is difficult to prove”.
Furthermore, an UpToDate review on “Approach to the patient with a scalp disorder” (Goldstein and Goldstein, 2017) does not mention narrow-band UVB as a therapeutic option.
Narrow-Band UVB Phototherapy for the Treatment of Cutaneous Mastocytosis
Brazzelli et al (2012) stated that mastocytoses represent a heterogeneous group of stem cell disorders marked by an abnormal hyperplasia and accumulation of mast cells in one or more tissues, including bone marrow, gastro-intestinal (GI) tract, liver, spleen, lymph nodes and skin. Indolent systemic mastocytosis (ISM) is characterized by red-brownish and pruriginous maculopapular lesions, a bone marrow infiltration without functional impairment and an indolent clinical course with a good prognosis. In particular, the most common cutaneous symptoms are urticarial rash and mild-to-high pruritus. These researchers analyzed the clinical outcome of patients affected by ISM with prevalent pruriginous cutaneous symptoms and a scarce response to antihistamines treated using narrowband ultraviolet B (NB-UVB) phototherapy, which was administered in a UV-irradiation cabin equipped with fluorescent UVB lamps with a peak emission at 311 to 313 nm. The perception of pruritus severity was examined using the visual analogue scale (VAS) before starting the treatment and at each control. A complete remission of the cutaneous lesions and pruritus was documented in all patients after a median of 40.3 UV treatments and a median cumulative dose of 51.4 J/cm(2), with a lasting remission over a 6-month follow-up. The median VAS score at the beginning of the treatment was 86.6 (SD = 6.64), whereas it decreased to 6.66 (SD = 3.75) after 3 months of therapy. The authors concluded that the findings of this study provided evidence that NB-UVB phototherapy was useful for the treatment of the cutaneous symptoms and pruritus in ISM.
Brazzelli et al (2016) noted that in mastocytosis, the skin is almost invariably involved, and cutaneous symptoms deeply affect patients' quality of life (QOL). In a retrospective, observational study, these researchers analyzed the outcomes of patients affected by cutaneous mastocytosis (CM) and ISM treated with phototherapy/photochemotherapy (PUVA or NB-UVB). For each patient, total numbers of PUVA or NB-UVB exposures, the cumulative UV dose (J/cm2 ), serum tryptase profile, and pruritus, before and after treatment, according to the VAS were considered. Skin lesions of each patient were examined, before and after treatment, according to a cutaneous scale score. A total of 20 patients affected by CM and ISM were studied; in particular, 10 patients received NB-UVB therapy, and other 10 patients received PUVA. A statistically significant mean reduction of pruritus in both groups (p < 0.01) was observed. The number of treatments needed to attain symptom relief was significantly lower in the PUVA group, but the mean exposure dose was significantly higher, if compared to the NB-UVB group. Serum tryptase levels showed a downward trend. The cutaneous score improved in both groups. The authors concluded that this study provided evidence that both NB-UVB and PUVA represent a safe and useful 2nd-line therapy of the cutaneous symptoms in mastocytosis. Moreover, these investigators stated that the drawbacks of this trial were that it was a retrospective study with a small sample size (n = 10 in each of the 2 treatment groups) and without a control group.
Furthermore, an UpToDate review on “Cutaneous mastocytosis: Treatment, monitoring, and prognosis” (Castells and Akin, 2020) states that “Psoralen-ultraviolet A therapy (PUVA) or narrow band UVB decreases the number of mast cells and controls pruritus that cannot be managed with antihistamines alone. However, long-term use is associated with an increased risk of skin cancer, and the skin lesions usually recur after therapy is stopped. Phototherapy may be considered for temporary symptomatic relief in patients with diffuse cutaneous mastocytosis with extensive skin involvement refractory to medical management”.
Phototherapy for the Treatment of Grover's Disease (Transient and Persistent Acantholytic Dermatosis)
An UpToDate review on “Grover's disease (transient and persistent acantholytic dermatosis)” (Riemann and High, 2020) recommends PUVA among third-line options for treatment. The review states that there are no published randomized clinical trials of therapies for Grover's disease, and that nearly all evidence for therapies comes from case series, case reports, and clinical experience. High-potency topical corticosteroids, moisturizers, and emollients are typically recommended as first-line therapy. The review does not mention narrowband UVB as a therapeutic option.
Phototherapy for the Treatment of Lymphomatoid Papulosis
Guidelines from the National Comprehensive Cancer Network (NCCN, 2020) state that, when managing patients with lymphomatoid papulosis, it is important to be reminded that this is not a malignant disorder, but a recurrent, benign, self-regressing lymphoid proliferation. Observation is preferred for patients with asymptomatic disease. Topical steroids and phototherapy (citing data on PUVA for lymphomatoid papulosis) are the most commonly used skin-directed therapies for initial treatment of limited lesions as well as extensive lesions. Systemtic therapy is indicated only for persons with extensive lesions.
Tan and Giam (2004) stated that lymphomatoid papulosis is a chronic benign disease that may be associated with malignant lymphomas. This case illustrated the relapsing and remitting nature of both lymphomatoid papulosis and its potential of developing cutaneous T-cell lymphoma; and NB-UVB phototherapy as a new modality of treatment of early-stage mycosis fungoides in these patients. A 44-year old woman has had recurrent crops of papules and nodules of lymphomatoid papulosis on her limbs for 15 years. Histological features ere consistent with the type B lesions of lymphomatoid papulosis. Eight years after the initial onset of these lesions she developed cutaneous T-cell lymphoma (mycosis fungoides). Since then, she has had recurrence of mycosis fungoides following the cessation of phototherapy; but had no evidence of systemic involvement. The lesions of lymphomatoid papulosis responded to intermittent courses of oral methotrexate. Mycosis fungoides was treated with oral psoralen and UVA phototherapy with good response. Unfortunately, the lesions relapsed, whenever phototherapy was discontinued. The most recent recurrence of mycosis fungoides was treated with NB-UVB therapy. The papules of lymphomatoid papulosis continued to appear but she remained free of lesions of mycosis fungoides 10 months following cessation of NB-UVB therapy. The authors concluded that long-term surveillance was essential in all cases of lymphomatoid papulosis as accurate predictors for the development of malignant lymphoma in these individuals are still lacking. Moreover, these researchers stated that it would be interesting to examine the long-term safety and effectiveness of NB-UVB as compared with PUVA in the treatment of mycosis fungoides in individuals with lymphomatoid papulosis.
An UpToDate review on “Lymphomatoid papulosis” (Kadin, 2020) states that “Narrowband UVB phototherapy or, if available, UVA1 (long-wave [340 to 400 nm] UVA) phototherapy, which do not require the oral or topical administration of psoralens, may be alternatives to PUVA. In one study, UVA1 phototherapy induced a complete response in 5 of 7 patients. Three patients relapsed between 1 and 20 months after discontinuation but responded to a second treatment cycle … For children with symptomatic lesions, scarring, or cosmetic concerns, we suggest topical corticosteroids or narrowband UVB therapy (Grade 2C)”.
Phototherapy (UVA and Narrow-Band UVB) for the Treatment of Uremic Pruritus
Simonsen and colleagues (2017) noted that uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by patients. The optimal treatments for uremic pruritus are not well defined. In a systematic review, these investigators reviewed the evidence on the various treatments for this condition; eligible subjects were adult patients with advanced CKD (stage greater than or equal to 3) or receiving any form of dialysis . PubMed, CINAHL, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and ClinicalTrials.gov from their inception to March 6, 2017, were systematically searched for RCTs of uremic pruritus treatments in patients with advanced CKD (stage greater than or equal to 3) or receiving any form of dialysis; 2 reviewers extracted data independently. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. Any intervention for the treatment of uremic pruritus was included. A quantitative change in pruritus intensity on a visual analog, verbal rating, or numerical rating scale. A total of 44 RCTs examining 39 different treatments were included in the review. These treatments included gabapentin, pregabalin, mast cell stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments. The largest body of evidence was found for the effectiveness of gabapentin. Due to the limited number of trials for the other treatments included, these researchers were unable to comment on their efficacy. Risk of bias in most studies was high. The authors concluded that despite the acknowledged importance of uremic pruritus to patients, with the exception of gabapentin, the current evidence for treatments is weak. They stated that large, simple, rigorous, multi-arm RCTs of promising therapies are urgently needed. The main drawbacks of this study were its heterogeneity in design, treatments, and outcome measures’ thus making comparisons difficult and precluded meta-analysis.
PUVA for the Treatment for Necrobiosis Lipoidica
Peckruhn and colleagues (2017) stated that necrobiosis lipoidica (NL) is a rare granulomatous disease of unclear etiology and is often seen in patients with diabetes. Characterized by its potential for ulcerations, it presents a serious burden for the afflicted patients. There are currently neither German nor European guidelines for the treatment of NL. At the same time, standard treatment with topical or intra-lesional corticosteroids does not always show satisfactory results. These researchers examined if the various therapeutic regimens published since 2000 have actually expanded the armamentarium in a relevant manner. Included were all publications that described more than 1 patient being treated with any given therapeutic modality. Overall, these investigators analyzed data for 16 different therapeutic regimens reported in 49 publications. The largest amount of data exists for topical PUVA therapy, photodynamic therapy (PDT), and systemic treatment with fumaric acid esters. However, this analysis showed that with an increase in the number of documented patients treated with a given therapeutic modality, the proportion of those achieving a complete response (CR) or partial response (PR) actually decreased. This was interpreted as publication bias. The authors concluded that no clear recommendation can be rendered for 2nd-line therapy in case topical or intra-lesional corticosteroids fail.
Furthermore, an UpToDate review on “Necrobiosis lipoidica” (Wanat and Rosenbach, 2017) stated that “For patients with nonulcerated necrobiosis lipoidica who cannot be managed adequately with local corticosteroids but still desire treatment, other interventions, such as topical tacrolimus, topical psoralen plus ultraviolet A (PUVA) photochemotherapy, systemic medications, and procedural therapies may be beneficial. Data to support the efficacy of these interventions are limited and insufficient for conclusions on the comparative efficacy of treatments”.
UVB for the Treatment of Kyrle Disease (Perforating Dermatosis)
An UpToDate review on “UVB therapy (broadband and narrowband)” (Honigsmann, 2019) states that “Acquired perforating dermatosis (APD, which encompasses Kyrle disease, acquired RPC, acquired PF, and acquired EPS and is often associated with underlying chronic renal failure or diabetes mellitus … Narrowband UVB is a low-cost treatment and may delay or avoid costly third-line treatments for many patients with inflammatory dermatoses”.
UVB for the Treatment of Papular Mucinosis
An UpToDate review on “Localized lichen myxedematosus” (Rongioletti, 2019) states that “Lichen myxedematosus (LM, also called papular mucinosis) is a chronic idiopathic cutaneous mucinosis characterized by lichenoid papules, nodules, and/or plaques; mucin deposition and a variable degree of fibrosis in the dermis; and an absence of associated thyroid disease … Localized LM is a benign condition for which treatment is not required. We typically reassure patients regarding the benign nature of localized LM and do not initiate treatment”.
UVB for the Treatment of Prurigo Nodularis
An UpToDate review on “Prurigo nodularis” (Watsky, 2019) states that “Patients with widespread or recalcitrant disease. Phototherapy -- For patients with widespread disease and for those with recalcitrant disease that does not respond to topical or intralesional corticosteroids, we suggest narrowband ultraviolet B (NBUVB) phototherapy as first-line therapy. NBUVB is administered 2 to 3 times weekly for up to 10 weeks in combination with topical corticosteroids. Oral antihistamines, the tricyclic antidepressants doxepin or amitriptyline, or gabapentin/pregabalin may be given as adjunctive treatment to control pruritus. Emollients and topical corticosteroids may also be used as needed. Psoralen plus ultraviolet A (PUVA) can be an alternative form of phototherapy if NBUVB is not available. Limited evidence for efficacy of phototherapy, including NBUVB, systemic and bath/topical PUVA, ultraviolet A1 (UVA1), and monochromatic 308 nm excimer light, for the treatment of PN is derived from small observational studies and a single randomized trial”.
UVB for the Treatment of Lichen Amyloidosis
An UpToDate review on “Cutaneous manifestations of amyloidosis” (Bohjanen and Miller, 2019) states that “Few studies have directly compared interventions, leaving uncertainty about relative efficacy. An open left-right comparison study that compared the efficacy of moderate to potent topical corticosteroids with the efficacy of ultraviolet B (UVB) or psoralen plus ultraviolet A (PUVA) phototherapy in 20 patients with a clinical diagnosis of lichen amyloidosis found a trend towards greater reductions in patient-reported itch and skin roughness with phototherapy, but the difference was not statistically significant … Treatment of primary localized cutaneous amyloidosis is not mandatory. Treatment is performed to improve symptoms and/or cosmesis. No treatment is consistently effective for macular amyloidosis and lichen amyloidosis. We suggest interventions to minimize pruritus and scratching as initial treatment (Grade 2C). Our initial treatment approach consists of local corticosteroid therapy to reduce pruritus. Other interventions that may be useful for patients who fail to improve with these conservative measures include phototherapy, laser, dermabrasion, and systemic medications”.
UVB for the Treatment of Refractory Uremic Pruritus
An UpToDate review on “Uremic pruritus” (Kobrin, 2020) states that ” Refractory pruritus -- Most patients with uremic pruritus will at least partially respond to emollients, topical analgesics and oral antihistamines or gabapentin. For patients who are refractory to these agents, ultraviolet B (UVB) phototherapy is a therapeutic option.”
Gilchrest et al (1977) examined the effect of ultraviolet (UV)-light phototherapy on severe persistent pruritus in 18 adult patients on hemodialysis. Patients were randomly assigned to 1 of 2 light sources. The experimental group received conventional sunburn-spectrum light (conventionally designated as UVB) in gradually increasing doses. The control group received time-matched exposures to long-wave ultraviolet (UV) light. All patients received 8 exposures to the entire skin surface over a 4-week treatment period; 9 of 10 patients in the sunburn-spectrum group reported marked decrease in pruritus as opposed to 2 of 8 in the placebo group (p < 0.01). Of those responding to sunburn-spectrum light, improvement usually occurred 2 to 3 weeks into treatment. Mild sunburn, noted by some patients in this group, was the only side effect . The response to phototherapy was unaffected by the presence of secondary hyperparathyroidism. The authors concluded that UV phototherapy was a safe, convenient, inexpensive and effective treatment for uremic pruritus. These researchers stated that these findings mandated further study of use of UVB in patients with uremic pruritis.
Ada et al (2005) reported the results of a pilot study of narrowband UVB (NB-UVB) phototherapy for the treatment of 20 patients with uremic pruritus; 10 patients completed the 6-week study period. A total of 8 patients were found to be responders. Of the remaining 10 patients who left the study before 6 weeks, 6 were satisfied with the response. In the follow-up period, 7 responders could be examined, and 3 were in remission 6 months after completing treatment. However, pruritus recurred in the remaining 4 responders. The authors concluded that NB-UVB phototherapy may be an effective treatment for patients with uremic pruritus; however, recurrence of pruritus was a frequent problem. Moreover, these researchers stated that randomized controlled trials (RCTs) are needed to better define the place of NB-UVB in the treatment protocol of this condition. In the meantime, these investigators were in the process of designing such a trial that would include 3 patient groups: one receiving NB UVB, and the others UVA (as a placebo) and broadband UVB (BB-UVB).
In a single-blind, randomized, controlled trial, Ko et al (2011) examined if NB-UVB phototherapy is an effective treatment for uremic pruritus. The treatment group received NB-UVB phototherapy 3 times/week for 6 weeks. The dose of NB-UVB started from 210 mJ cm(-2) and was increased by 10% each time. The control group received time-matched exposures to long-wave UVA radiation. A visual analog scale (VAS) score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6 weeks of phototherapy. Both the NB-UVB and control groups had significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow-up. Compared with the control group, the NB-UVB group showed a significant improvement in the involved body surface area (BSA) affected by pruritus (p = 0·006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB-UVB group had lower pruritus intensity scores at week 6, week 10 and week 12. This may indicate a beneficial difference at certain time-points, but the effect appeared marginal. The authors concluded that NB-UVB phototherapy did not show a significant effect in reducing pruritus intensity compared with a control group for refractory uremic pruritus. These researchers stated that further studies are needed.
NB-UVB Phototherapy for the Treatment of Cutaneous Mastocytosis
Brazzelli et al (2012) stated that mastocytoses represent a heterogeneous group of stem cell disorders marked by an abnormal hyperplasia and accumulation of mast cells in one or more tissues, including bone marrow, gastro-intestinal (GI) tract, liver, spleen, lymph nodes and skin. Indolent systemic mastocytosis (ISM) is characterized by red-brownish and pruriginous maculopapular lesions, a bone marrow infiltration without functional impairment and an indolent clinical course with a good prognosis. In particular, the most common cutaneous symptoms are urticarial rash and mild-to-high pruritus. These researchers analyzed the clinical outcome of patients affected by ISM with prevalent pruriginous cutaneous symptoms and a scarce response to antihistamines treated using narrowband ultraviolet B (NB-UVB) phototherapy, which was administered in a UV-irradiation cabin equipped with fluorescent UVB lamps with a peak emission at 311 to 313 nm. The perception of pruritus severity was examined using the visual analogue scale (VAS) before starting the treatment and at each control. A complete remission of the cutaneous lesions and pruritus was documented in all patients after a median of 40.3 UV treatments and a median cumulative dose of 51.4 J/cm(2), with a lasting remission over a 6-month follow-up. The median VAS score at the beginning of the treatment was 86.6 (SD = 6.64), whereas it decreased to 6.66 (SD = 3.75) after 3 months of therapy. The authors concluded that the findings of this study provided evidence that NB-UVB phototherapy was useful for the treatment of the cutaneous symptoms and pruritus in ISM.
Brazzelli et al (2016) noted that in mastocytosis, the skin is almost invariably involved, and cutaneous symptoms deeply affect patients' quality of life (QOL). In a retrospective, observational study, these researchers analyzed the outcomes of patients affected by cutaneous mastocytosis (CM) and ISM treated with phototherapy/photochemotherapy (PUVA or NB-UVB). For each patient, total numbers of PUVA or NB-UVB exposures, the cumulative UV dose (J/cm2 ), serum tryptase profile, and pruritus, before and after treatment, according to the VAS were considered. Skin lesions of each patient were examined, before and after treatment, according to a cutaneous scale score. A total of 20 patients affected by CM and ISM were studied; in particular, 10 patients received NB-UVB therapy, and other 10 patients received PUVA. A statistically significant mean reduction of pruritus in both groups (p < 0.01) was observed. The number of treatments needed to attain symptom relief was significantly lower in the PUVA group, but the mean exposure dose was significantly higher, if compared to the NB-UVB group. Serum tryptase levels showed a downward trend. The cutaneous score improved in both groups. The authors concluded that this study provided evidence that both NB-UVB and PUVA represent a safe and useful 2nd-line therapy of the cutaneous symptoms in mastocytosis. Moreover, these investigators stated that the drawbacks of this trial were that it was a retrospective study with a small sample size (n = 10 in each of the 2 treatment groups) and without a control group.
Furthermore, an UpToDate review on “Cutaneous mastocytosis: Treatment, monitoring, and prognosis” (Castells and Akin, 2021) states that “Psoralen-ultraviolet A therapy (PUVA) or narrow band UVB decreases the number of mast cells and controls pruritus that cannot be managed with antihistamines alone. However, long-term use is associated with an increased risk of skin cancer, and the skin lesions usually recur after therapy is stopped. Phototherapy may be considered for temporary symptomatic relief in patients with diffuse cutaneous mastocytosis with extensive skin involvement refractory to medical management”.
NB-UVB Phototherapy for the Treatment of Drug-Related Hypersensitivity Reaction
An UpToDate review on “UVB therapy (broadband and narrowband)” (Honigsmann, 2021) does not mention drug-related hypersensitivity reaction as an indication for UVB therapy.
NB-UVB Phototherapy for the Treatment of Erythema Annulare Centrifugum
Reuter et al (2007) noted that erythema annulare centrifugum is an acute dermatosis of unclear etiology, which presents with annular erythematous lesions with marginal scale. Therapeutically, systemic and topical glucocorticoids are used primarily. These investigators treated a patient with large lesions in the area of the thighs resistant to a therapy with topical glucocorticoids, with topical calcitriol in combination with 311-nm narrow band ultraviolet B (NB-UVB) phototherapy. After 4 weeks of treatment the skin lesions had cleared nearly completely without any side effects. The combination topical vitamin D3-analog calcitriol and 311-nm NB-UVB phototherapy was effective and can be regarded as a useful alternative to glucocorticoids for the treatment of erythema annulare centrifugum. This was a single-case study; and its findings were confounded by the combined use of topical glucocorticoids, topical calcitriol, and NB-UVB.
Furthermore, an UpToDate review on “Erythema annulare centrifugum” (Haeberle, 2021) does not mention NB-UVB as a management / therapeutic option.
NB-UVB Phototherapy for the Treatment of Lichen Sclerosus
Petersen et al (2018) stated that radiation induced morphea (RIM) is an increasingly common complication of radiation treatment for malignancy as early detection has made more patients eligible for non-surgical therapeutic options. In many cases, the radiation oncologist is the first person to learn of the initial skin changes, often months before a dermatologist sees them. These researchers presented the case of a breast cancer patient who developed a rare bullous variant of RIM, which delayed her diagnosis and subsequent treatment. It is imperative to diagnose RIM early as it carries significant morbidity and permanent deformity if left untreated. The lesions typically present within 1 year of radiation therapy and extend beyond the radiated field. RIM is often mistaken for radiation dermatitis or cellulitis. Bullae, when present, are often hemorrhagic in appearance, which can serve as another clinical clue. It is important to refer these patients for a full gynecologic examination as there can be concurrent anogenital lichen sclerosus et atrophicus, which is both debilitating and carries a long-term risk for squamous cell carcinoma. Treatment with systemic agents is often necessary, and can be managed by a dermatologist. The most proven regimen in the literature appeared to be methotrexate, with or without concurrent narrow-band UVB phototherapy.
The British Association of Dermatologists’ guidelines on “Management of lichen sclerosus” (Lewis et a, 2018) did not have a recommendation for ultraviolet light therapy.
Furthermore, an UpToDate review on “Vulvar lichen sclerosus” (Cooper and Arnold, 2021) does not mention narrow-band ultraviolet B (NB-UVB) as a management / therapeutic option.
NB-UVB Phototherapy for the Treatment of Lichenoid Dermatitis
An UpToDate review on “Lichenoid drug eruption (drug-induced lichen planus)” (Ziemer, 2021) states that “Lichenoid granulomatous dermatitis is a histopathologic reaction pattern with vacuolar alteration of the basal layer with necrotic keratinocytes and a chronic, inflammatory infiltrate consisting of lymphocytes, eosinophils, plasma cells, and macrophages forming variable types of granulomas. In more than one-third of the cases, the most common clinical correlates are drug eruptions … A special and rare subtype is giant cell lichenoid dermatitis, a rare condition considered an unusual variant of lichenoid drug eruption or a manifestation of sarcoidosis. Histopathologic findings include multinucleated giant cells … For patients with symptomatic disease involving a limited skin area (e.g., the extremities), we suggest topical corticosteroids rather than oral corticosteroids (Grade 2C). We generally use a super-potent topical corticosteroid (e.g., clobetasol propionate 0.05 %) ointment or cream twice daily for 2 to 4 weeks. Less potent topical corticosteroids, such as mometasone furoate 0.1 % ointment or cream, can be used for facial lesions … For patient with oral erosive lichenoid drug eruption, we suggest topical corticosteroids as first line treatment (Grade 2B). We typically use clobetasol propionate 0.05 % ointment 2 or 3 times per day for 4 to 8 weeks”. However, narrow-band UVB is not mentioned as a therapeutic option.
NB-UVB Phototherapy for the Treatment of Lymphomatoid Papulosis
In a case report, Tan and Giam (2004) reported on the findings of a 44-year-old woman with recurrent crops of papules and nodules of lymphomatoid papulosis and who had early-stage mycosis fungoides. The lesions of lymphomatoid papulosis responded to intermittent courses of oral methotrexate. Mycosis fungoides was treated with oral psoralen and ultraviolet A phototherapy with good response. Unfortunately, the lesions relapsed, whenever phototherapy was discontinued. The most recent recurrence of mycosis fungoides was treated with NB-UVB therapy. The papules of lymphomatoid papulosis continued to appear but she remained free of lesions of mycosis fungoides 10 months after cessation of NB-UVB therapy.
Furthermore, an UpToDate review on “Lymphomatoid papulosis” (Kadin, 2021) states that “For children with symptomatic lesions, scarring, or cosmetic concerns, we suggest topical corticosteroids or narrowband UVB therapy (Grade 2C)”.
Contraindications to Ultraviolet Phototherapy
An evidence-based analysis on “Ultraviolet phototherapy management of moderate-to-severe plaque psoriasis” (Medical Advisory Secretariat, 2009) noted that there are a range of contraindications for UVB phototherapy and for PUVA. Both treatments have contraindications including any history of light sensitivity disorders (i.e., lupus erythematosus, porphyria, cutanea tarda, xeroderma pigmentosum etc.), melanoma, squamous cell carcinoma, aphakia, and/or basal cell carcinoma. The safety for PUVA has also not been established in pregnancy, nursing mothers, or children. There are also contraindications for patients with significant hepatic impairment and for those taking warfarin or phenytoin.
An UpToDate review on “UVA1 phototherapy” (Krutmann and Morita, 2019) states that “Ultraviolet A1 (UVA1) phototherapy is contraindicated in patients with xeroderma pigmentosum, porphyria, melanoma and nonmelanoma skin cancer, and in patients on long-term immunosuppressive therapy (e.g., after organ transplantation). UVA1 phototherapy should not be used for patients with UVA-sensitive photodermatoses or photosensitive atopic dermatitis or patients taking photosensitizing drugs. The efficacy and long-term safety of UVA1 therapy has not been evaluated and therefore should be used with caution in patients younger than 18 years”.
An UpToDate review on “UVB therapy (broadband and narrowband)” (Honigsmann, 2019) lists lupus erythematosus and xeroderma pigmentosum as absolute contraindications as well as history of photosensitivity diseases (e.g., chronic actinic dermatitis, solar urticaria), history of melanoma, history of nonmelanoma skin cancer, history of treatment with arsenic or ionizing radiation because of the increased risk for skin cancer, and immunosuppression for organ transplant patients as relative contraindications.
Home Phototherapy (UVB) for the Treatment of Atopic Dermatitis (Eczema)
An UpToDate review on “Treatment of atopic dermatitis (eczema)” (Weston and Howe, 2020) does not mention home phototherapy as a management option.
Guidelines from the American Academy of Dermatology guidelines of care for the management of atopic dermatitis (Sidbury, et al., 2014) states that home phototherapy under the direction of a physician may be considered for patients who are unable to receive phototherapy in an office setting. The guidelines state that, although there are no studies that document the efficacy or safety of home light therapy for patients with atopic dermatitis, or that contrast its use to in-office phototherapy, results similar to home phototherapy for psoriasis might be expected.
Home Phototherapy for the Treatment of Cutaneous T-Cell Lymphoma (Mycosis Fungoides and Sezary Syndrome)
Milstein et al (1982) described the findings of 31 patients with early mycosis fungoides (MF) and 3 patients with parapsoriasis en plaques who were treated with ultraviolet (UV) phototherapy (280 to 350 nm) at home using a commercially available light source containing 4 Westinghouse FS40 lamps. A complete clinical and histologic remission of disease, lasting for a median duration in excess of 18 months, was achieved in 19 patients (61 %) with MF. Although higher complete response rates generally were achieved with other therapeutic modalities, UV phototherapy with its minimal adverse effects may be indicated for selected patients. Moreover, the authors concluded that controlled studies are needed to examine the full potential of conventional phototherapy in the management of MF.
Resnik et al (1993) noted that in 1982, they reported their preliminary observations on the use of home UV phototherapy for patch and early plaque phase MF. These researchers presented follow-up data of the original 31 patients, covering an interval of up to 15 years. All patients used a commercially available UV phototherapy unit that contained 4 Westinghouse FS40 fluorescent lamps for daily exposures of their non-sun-exposed skin regions. A complete clinical and histologic response to home phototherapy occurred in 23 patients (74 %) with a maximum duration of the response from 5 months to more than 15 years (median of 51 months). After maintenance phototherapy was discontinued, 7 patients (23% ) had a sustained disease-free interval lasting more than 58 months (median of greater than 90 months). This indicated that cure may have been achieved in a minority of patients. Phototherapy was well-tolerated without evidence of significant photo-damage or photo-carcinogenicity. The authors concluded that these findings indicated that home phototherapy may be a therapeutic option for treatment of selected patients with early MF.
In a review on “Phototherapy of mycosis fungoides” (Hodak and Pavlovsky, 2015), home phototherapy is not mentioned as therapeutic option.
A consensus statement of the United States Cutaneous Lymphoma Consortium on “Guidelines for phototherapy of mycosis fungoides and Sezary syndrome” (Olsen et al, 2016) noted that broadband-UVB, both home- and office-based, has been demonstrated to be safe but has fallen out of favor as demonstrated by a recent survey of cutaneous lymphoma experts, being largely supplanted by NB-UVB.
An UpToDate review on “Treatment of early stage (IA to IIA) mycosis fungoides” (Hoppe et al, 2021) states that “Both narrow-band ultraviolet B (NBUVB, 311 nm wavelength) and broad-band (BBUVB; 290 to 320 nm wavelength) have been used as skin-directed treatments for early-stage MF, although BBUVB emitting sources have mostly been replaced by NBUVB lamps worldwide. In retrospective cohort studies, NBUVB has demonstrated superior efficacy and decreased toxicity compared with BBUVB, but not PUVA, with complete response rates ranging from 54 to 90 %. However, there are no randomized trials evaluating the relative efficacy of these phototherapy modalities in patients with early-stage MF … NBUVB phototherapy is administered in a dermatology office 3 to 5 times per week with gradual incremental dose delivery. Improvement is generally seen after 20 to 40 treatments. After a complete response is achieved, the frequency of therapy is tapered very slowly during the maintenance period and then discontinued. The tapering schedule is non-standardized and differs by institution. As an example of a slow taper, after a complete response or plateau in response, treatments may be decreased from 3 times a week to twice-weekly for 1 to 2 months, then decreased to once-weekly for 1 to 2 months, followed by discontinuation of therapy”. This UTD review does not mention home phototherapy as a therapeutic option
Furthermore, National Comprehensive Cancer Network’s clinical practice guideline on “T-cell lymphomas” (Version 1.2022) does not mention phototherapy / UVB as a management option.
Narrow-Band UVB Phototherapy for COVID-19
Lau et al (2022) stated that COVID-19 morbidity and mortality are driven by poor immune regulation. NB-UVB phototherapy is standard of care (SOC) in a number of immune-dysregulated diseases. In a prospective, randomized, double-blinded, placebo-controlled, multi-center study, these researchers examined the effectiveness of NB-UVB phototherapy for improving outcomes in high-risk, hospitalized COVID-19 patients; the pilot phase results were reported here. Consecutive patients admitted with a positive COVID-19 PCR were screened for eligibility. Enrolled subjects were computer-randomized 1:1 to NB-UVB or placebo phototherapy. Participants were treated daily with escalating doses on 27 % of their body surface area for up to 8 consecutive days. Primary outcomes were safety and effectiveness, defined as persistent or painful erythema and 28-day mortality. Comparisons were made via non-parametric exact tests. Patients in treatment (n = 15) and placebo (n = 15) arms had similar demographics. No AEs occurred. The 28-day mortality was 13.3 % in treatment versus 33.3 % in placebo arms (p = 0.39). NB-UVB phototherapy in hospitalized COVID-19 patients was safe. Decreased mortality was observed in treated patients; however, this was statistically non-significant. The authors concluded that given its low-cost, scalability, and adjunctive nature, NB-UVB has the potential to improve COVID-19 outcomes. These researchers stated that continuation of this trial is needed.
These investigators stated that as the pilot phase of a larger clinical trial, this study was under-powered to detect statistically significant differences in clinical outcomes between treatment arms. The statistical power for a Fisher's exact test with 15 patients per group given the rates of 28‐day mortality observed in this pilot was 14.1 %. This power calculation will be used to refine the biostatistical considerations for the planned, larger clinical trial.
Narrow-Band UVB Phototherapy for Extensive Lymphomatoid Papulosis, Multiple Erythematous Hyper-Pigmented Macules / Papules
Tan and Giam (2004) noted that lymphomatoid papulosis (LyP) is a chronic benign disease that may be associated with malignant lymphomas. This single-case study reported the relapsing and remitting nature of both LyP and its potential of developing cutaneous T-cell lymphoma and NB-UVB phototherapy as a new modality of treatment of early-stage mycosis fungoides in these patients. This case entailed a 44-year-old woman who has had recurrent crops of papules and nodules of LyP on the limbs for 15 years. Histological features were consistent with the type B lesions of LyP. Eight years after the initial onset of these lesions she developed cutaneous T-cell lymphoma (mycosis fungoides). Since then, she has had recurrence of mycosis fungoides following the cessation of phototherapy; but exhibited no evidence of systemic involvement. The lesions of LyP responded to intermittent courses of oral methotrexate. Mycosis fungoides was treated with oral psoralen and UVA phototherapy with good response. Unfortunately, the lesions relapsed, whenever phototherapy was discontinued. The most recent recurrence of mycosis fungoides was treated with NB-UVB therapy. The papules of LyP continued to appear but she remained free of lesions of mycosis fungoides 10 months following cessation of NB-UVB therapy. The authors concluded that long-term surveillance is essential in all cases of LyP as accurate predictors for the development of malignant lymphoma in these individuals are still lacking.
de Souza et al (2009) stated that LyP is a cyclic papulonodular eruption that is clinically benign and histologically malignant. Association with hematologic neoplasia has been reported in 5 % to 20 % of all cases. In a retrospective study, these investigators reviewed the clinical and histopathologic features of LyP in pediatric patients. They searched for the records of all patients with a clinical and histopathologic diagnosis of LyP seen at the authors’ clinic from January 1991 through April 2008. The cases of pediatric patients (aged less than 20 years) were reviewed in detail. Of 123 patients with LyP identified, 14 (11 %) were in the pediatric age group. Most were male (64 %); mean age of onset was 12 years. Type A LyP was identified in 12 patients, 1 patient had type B, and none had type C (type not determined in 1case). A total of 10 cases showed CD8 predominance by immunohistochemistry. T-cell intracytoplasmic antigen staining was positive in 3 cases of CD8(+) LyP type A and the 1 case of LyP type B. Lesional T-cell receptor gene re-arrangement studies were negative in 9 of 10 patients with LyP type A. The average follow-up time was 5.5 years. Lesions improved with treatment in most cases, and none of the cases was associated with hematologic malignancies. The authors concluded that among their pediatric patients, these investigators noted a predominance of CD8(+) LyP, which did not appear to have an aggressive course. Moreover, these researchers stated that further longitudinal studies are needed to examine prognostic differences between CD4(+) and CD8(+) LyP and their biological significance. The authors stated that the main drawbacks of this study were its retrospective design and its small sample size (n = 14 pediatric subjects).
Coelho et al (2010) noted that LyP is a rare skin lympho-proliferative disorder that has been reported only rarely in children. It is included in the World Health Organization (WHO) classification of cutaneous lymphomas. These investigators reported a case of LyP in a 13-year-old Caucasian girl who presented with a 6-month history of recurrent papular lesions on the left upper arm. Histopathologic examination showed a diffuse cellular infiltration of small and medium-sized T lymphocytes CD30+ in the superficial dermis. Treatment was started using a UVB phototherapy handpiece (twice-weekly), with resolution of the lesions after 6 weeks of treatment. There was a relapse after 9 months with a good response after 6 more sessions of treatment. The patient was in good health without lesions after 12 months of follow-up.
Zheng et al (2014) attempted to improve the level of diagnosis and differential diagnosis of LyP. Two cases of type B LyP were identified; and the literature was reviewed to summarize the clinical outcomes and pathology of LyP and its treatment. The 2 patients exhibited symptoms with papulonodular lesions, the centers of which gradually underwent ulceration and necrosis. CD30, a helper T-cell marker specifically expressed in tumor cells was analyzed by immunohistochemical (IHC) staining and the result showed that CD30-negative or only scattered CD30-positive cells were present; thus, a diagnosis of type B LyP was made. A fairly good curative effect was achieved following treatment with retinoic acid, glucocorticoids and immunomodulatory drugs. The authors concluded that LyP is a type of low-level malignant lymphoma and is easily misdiagnosed as pityriasis lichenoides et varioliformis acuta and other diseases. In order to avoid under-diagnosis and misdiagnosis, physicians should examine suspected patients by histopathological and IHC examination.
Furthermore, an UpToDate review on “Lymphomatoid papulosis” (Kadin, 2022) states that “For patients with extensive or symptomatic disease, scarring, or cosmetic concerns, we suggest low-dose methotrexate as the initial therapy (Grade 2C) … For patients for whom methotrexate is contraindicated and for patients with LyP that does not respond to methotrexate, we suggest psoralen and ultraviolet A (PUVA) therapy (Grade 2C). PUVA is administered twice weekly for 6 to 8 weeks or until clearance … For children with symptomatic lesions, scarring, or cosmetic concerns, we suggest topical corticosteroids or narrowband ultraviolet B (NBUVB) therapy (Grade 2C). Low-dose methotrexate (2.5 to 15 mg per week) may be an alternative for children who do not respond to topical steroids or ultraviolet B (UVB)”.
Narrow-Band UVB Phototherapy for Hypersensitive Rash
Tan and Foley (2004) reported on the case of a 23-year-old man who presented with the onset of a widespread pruritic eruption 4 days after ingestion of an Ecstasy tablet for the 1st time. The rash was characterized by small papules up to 10-mm in diameter distributed in a guttate pattern over most of his body and displaying the Kobner phenomena. Histology diagnosed a psoriasiform drug eruption. The eruption was not responsive to the initial treatment of topical betamethasone dipropionate 0.1 % ointment and oral prednisolone. Prompt resolution was achieved with NB-UVB phototherapy and avoidance of re-challenge. The main drawbacks of this trial were that this was a single-case study; and the hypersensitive rash was caused by the ingestion of an Ecstasy tablet.
Furthermore, UpToDate reviews on “Overview of dermatitis (eczematous dermatoses)” (Howe, 2022) and “Overview of cutaneous lupus erythematosus” (Merola, 2022) do not mention the use of NB-UVB as a management / therapeutic option.
Narrow-Band UVB Phototherapy for Pityriasis Lichenoides Chronica
In a systematic review, Bellinato et al (2019) examined the treatments of patients with pityriasis lichenoides (PL). These investigators carried out a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies examining PL treatment including 3 or more subjects and published in English between January 1, 1970 and April 15, 2019. A total of 441 studies were screened, and 37 original manuscripts meeting the inclusion and exclusion criteria were identified, including 12 case-series studies, 18 reviews, 4 prospective studies, 2 comparative studies and 1 RCT. In most studies, UV phototherapy (NB-UVB, broadband UVB, UVA1 or PUVA) was employed. Clearance rates with the different modalities were hardly comparable between different studies, ranging approximately between 70 % and 100 %. NB-UVB showed an effectiveness similar to PUVA as such as the combination of UVA and UVB versus PUVA. Oral erythromycin showed clearance rates ranging between 66 % and 83 %, whereas methotrexate up to 100 % but in small and dated studies. Evidence for other treatments was scarce. There was a lack of high level of evidence studies on PL treatment. The interpretation of the results was biased by the possible auto-resolution of the disease, the sample heterogeneity between children and adults and the short follow-up period of the studies. Only some studies examined how results were durable following cessation of therapy; QOL and the impact of treatment were never assessed. The authors suggested that NB-UVB phototherapy as 1st-line treatment. Oral erythromycin with or without topical corticosteroids and low-dose methotrexate as 2nd-line therapies.
Furthermore, an UpToDate review on “Pityriasis lichenoides chronica” (Musiek, 2022) states that “Narrowband ultraviolet B (NBUVB), broadband ultraviolet B (UVB), and psoralen plus ultraviolet A (PUVA) are the primary phototherapeutic modalities used to treat these diseases. We favor use of UVB phototherapy based upon the more favorable safety profile compared with PUVA photochemotherapy”.
Narrowband-UVB (NB-UVB) for the Treatment of Darier disease
Reuter et al (2007) stated that erythema annulare centrifugum Darier is an acute dermatosis of unclear etiology, which presents with annular erythematous lesions with marginal scale. Therapeutically, systemic and topical glucocorticoids are used primarily. These researchers treated a patient with large lesions around the thighs resistant to a therapy with topical glucocorticoids, with topical calcitriol in combination with 311-nm NB-UVB phototherapy. After 4 weeks of treatment the skin lesions had cleared nearly completely without any side effects. The authors concluded that the combination topical vitamin D3-analog calcitriol and 311-nm NB-UVB phototherapy was effective and could be regarded as a useful alternative to glucocorticoids for erythema annulare centrifugum Darier. This was a single-case study; and its findings were confounded by the combined use of topical glucocorticoids, with topical calcitriol in combination with NB-UVB phototherapy.
Furthermore, an UpToDate review on “Darier disease” (Hohl, 2023) does not mention NB-UVB as a therapeutic options.
NB-UVB for the Treatment of Disseminated Superficial Actinic Porokeratosis
There is a lack of evidence to support the use of NB-UVB for the treatment of disseminated superficial actinic porokeratosis (DSAP). In fact, several studies have reported that exposure to NB-UVB may result in DSAP.
Kawara et al (2011) noted that DSAP is a subtype of porokeratosis, thought to be clonal disorder of keratinization. Chronic exposure to UV light might be an etiological cause of DSAP, of which frequent sites are sun-exposed areas. These investigators reported on a case of DSAP that occurred on the trunk of a 79-year-old man with psoriasis treated with NB-UVB for clearing and maintenance therapies. The authors stated that DSAP has been reported to be associated with psoralen and UVA therapy and broadband UVB, but not NB-UVB; and this may be the 1st case of DSAP after repeated exposure to NB-UVB.
Zhao et al (2016) stated that MF is the most common form of primary cutaneous T cell lymphoma; and NB-UVB is used increasingly in the treatment of patients with MF because of its good toleration and well-established management. These investigators discussed the risk factors and underlying pathogenic factors in the patients with secondary skin diseases following NB-UVB therapy. They reported in detail the 1st case of a patient with MF accompanied with AK, AK with squamous cell carcinoma (SCC) transformation and porokeratosis following NB-UVB therapy. Meanwhile, sequence variants in tumor suppressor p53 gene in the patient's specimens were detected. These researchers carried out a literature search using the key word "narrowband ultraviolet B light" and "side effects" on PubMed; and 14 cases of this entity were found. A total of 15 patients including the authors’ case were reviewed in this study. The mean age at diagnosis of secondary skin dermatoses following NB-UVB therapy was 62.08 years with a male:female ratio of 2:1. The cases were reported more in Europeans than in Asians (2.75:1), and the Fitzpatrick skin type was mainly Ito III (12/15). The mean cumulative number and cumulative dose of UVB treatments were 43.71 and 42, 400 (mJ/cm), respectively. There was a positive relationship between Fitzpatrick skin type and cumulative dose of UVB treatments. Among the secondary skin diseases after NB-UVB treatment, 12 were tumors, 2 were non-tumorous dermatoses. Only the authors’ patient presented with both. By polymerase chain reaction-single nucleotide polymorphism (PCR-SNP) analysis, C-G mutation of exon 4 of p53 was found in AK and MF specimens in this patient. The authors concluded that to their knowledge, this case was the 1st MF patient accompanied with AK, AK with SCC transformation and porokeratosis following NB-UVB treatment. Lower Fitzpatrick skin type may be the risk factor of secondary skin diseases following NB-UVB treatment.
Sim et al (2018) noted that porokeratosis is a rare epidermal disorder characterized by annular or linear hyperkeratotic plaques with slightly raised thread-like borders, and in most cases, atrophic centers. Disseminated superficial porokeratosis and DSAP, which primarily entail sun-exposed areas, are common types of porokeratoses. Histologically, a column of parakeratotic cells, a so-called cornoid lamella, is a hallmark of porokeratosis. Porokeratosis is considered to result from the inability to eliminate an abnormal keratinocyte clone induced by genetic factors and various stimuli, including sunlight, artificial UV light, viral infections, immune-suppressive conditions (hematologic malignancies, organ transplants, or autoimmune disease), and immune-suppressive therapies. These investigators reported on the case of a 59-year-old woman with DSAP that developed following NB-UVB therapy for psoriasis. The authors concluded that this case emphasized the occurrence of DSAP due to NB-UVB that is able to induce local immunosuppression at the irradiated site; the pathogenesis of DSAP remains unclear.
Furthermore, an UpToDate review on “Porokeratosis” (Imhof et al, 2023) does not mention NB-UVB as a therapeutic option for DSAP.
References
The above policy is based on the following references:
- Ada S, Seçkin D, Budakoğlu I, Ozdemir FN. Treatment of uremic pruritus with narrowband ultraviolet B phototherapy: An open pilot study. J Am Acad Dermatol. 2005;53(1):149-151.
- Alabdulkareem AS, Abahussein AA, Okoro A. Minimal benefit from photochemotherapy for alopecia areata. Int J Dermatol. 1996;35(12):890-891.
- American Academy of Dermatology Committee on Guidelines of Care. Guidelines of care for phototherapy and photochemotherapy. J Am Acad Dermatol. 1994;31(4):643-648.
- American Academy of Dermatology (AAD). Psoriasis: Recommendations for UVB combination therapies. Practice Management Center. 2018. Available at: https://www.aad.org/practicecenter/quality/clinical-guidelines/psoriasis/phototherapy-and-photochemotherapy/uvb-combination-therapies. Accessed July 19, 2018.
- Archier E, Devaux S, Castela E, et al. Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: A systematic literature review. J Eur Acad Dermatol Venereol. 2012;26 Suppl 3:11-21.
- Bandow GD, Koo JY. Narrow-band ultraviolet B radiation: A review of the current literature. Int J Dermatol. 2004;43(8):555-561.
- Beani JC, Jeanmougin M. Narrow-band UVB therapy in psoriasis vulgaris: Good practice guideline and recommendations of the French Society of Photodermatology. Ann Dermatol Venereol. 2010;137(1):21-31.
- Beattie PE, Dawe RS, Ibbotson SH, Ferguson J. UVA1 phototherapy for treatment of necrobiosis lipoidica. Clin Exp Dermatol. 2006;31(2):235-238.
- Bellinato F, Maurelli M, Gisondi P, et al. A systematic review of treatments for pityriasis lichenoides. J Eur Acad Dermatol Venereol . 2019;33(11):2039-2049.
- Berg M, Ros AM, Berne B. Ultraviolet A phototherapy and trimethylpsoralen UVA photochemotherapy in polymorphous light eruption -- a controlled study. Photodermatol Photoimmunol Photomed. 1994;10(4):139-143.
- Bishnoi A, Parsad D, Vinay K, Kumaran MS. Phototherapy using narrowband ultraviolet B and psoralen plus ultraviolet A is beneficial in steroid-dependent antihistamine-refractory chronic urticaria: A randomized, prospective observer-blinded comparative study. Br J Dermatol. 2017;176(1):62-70.
- Bohjanen K, Miller DD. Cutaneous manifestations of amyloidosis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2019.
- Brodell RT. Granuloma annulare: Management. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed August 2023.
- Brazzelli V, Grassi S, Merante S, et al. Narrow-band UVB phototherapy and psoralen-ultraviolet A photochemotherapy in the treatment of cutaneous mastocytosis: A study in 20 patients. Photodermatol Photoimmunol Photomed. 2016;32(5-6):238-246.
- Brazzelli V, Grasso V, Manna G. Indolent systemic mastocytosis treated with narrow-band UVB phototherapy: Study of five cases. J Eur Acad Dermatol Venereol. 2012;26(4):465-469.
- Brenner M, Herzinger T, Berking C, et al. Phototherapy and photochemotherapy of sclerosing skin diseases. Photodermatol Photoimmunol Photomed. 2005;21(3):157-165.
- Calzavara-Pinton P, Venturini M, Sala R. Medium-dose UVA1 therapy of lymphomatoid papulosis. J Am Acad Dermatol. 2005;52(3):530-532.
- Castells MC, Akin C. Cutaneous mastocytosis: Treatment, monitoring, and prognosis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2020; December 2021.
- Cather J, Menter A. Novel therapies for psoriasis. Am J Clin Dermatol. 2002;3(3):159-173.
- Chalmers RJG, O'Sullivan T, Owen CM, Griffiths CEM. Interventions for guttate psoriasis. Cochrane Database Syst Rev. 2000;(2):CD001213.
- Chan ES-Y, Thornhill M, Zakrzewska J. Interventions for treating oral lichen planus. Cochrane Database Syst Rev. 1999;(2):CD001168.
- Chen X, Yang M, Cheng Y, et al. Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis. Cochrane Database Syst Rev. 2013;10:CD009481.
- Choi YM, Adelzadeh L, Wu JJ. Photodynamic therapy for psoriasis. J Dermatolog Treat. 2015;26(3):202-207.
- Claes C, Kulp W, Greiner W, et al. Therapy of moderate and severe psoriasis [summary]. HTA Report. Cologne, Germany: German Agency for Health Technology Assessment at the German Institute for Medical Documentation and Information (DAHTA) (DIMDI); 2006.
- Clark C, Dawe RS, Evans AT, et al. Narrowband TL-01 phototherapy for patch-stage mycosis fungoides. Arch Dermatol. 2000;136:748-752.
- Coelho JD, Afonso A, Feio AB. Regional lymphomatoid papulosis in a child -- treatment with a UVB phototherapy handpiece. J Cosmet Laser Ther. 2010;12(3):155-156.
- Collins P, Ferguson J. Narrow-band UVB (TL-01) phototherapy: An effective preventative treatment for the photodermatoses. Br J Dermatol. 1995;132(6):956-963.
- Cooper SM, Arnold SJ. Vulvar lichen sclerosus. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2021.
- Cooper SM, Burge SM. Darier's disease: Epidemiology, pathophysiology, and management. Am J Clin Dermatol. 2003;4(2):97-105.
- Cyr PR. Diagnosis and management of granuloma annulare. Am Fam Physician. 2006;74(10):1729-1734.
- Davis MD, McEvoy MT, el-Azhary RA. Topical psoralen-ultraviolet A therapy for palmoplanar dermatoses: Experience with 35 consecutive patients. Mayo Clin Proc. 1998;73(5):407-411.
- De Rie MA, Sommer A, Hoekzema R, Neumann HA. Treatment of necrobiosis lipoidica with topical psoralen plus ultraviolet A. Br J Dermatol. 2002;147(4):743-747.
- de Souza A, Camilleri MJ, Wada DA, et al. Clinical, histopathologic, and immunophenotypic features of lymphomatoid papulosis with CD8 predominance in 14 pediatric patients. J Am Acad Dermatol. 2009;61(6):993-1000.
- Delrosso G, Bornacina C, Farinelli P, et al. Bath PUVA and psoriasis: Is a milder treatment a worse treatment? Dermatology. 2008;216(3):191-193.
- Der-Petrossian M, Seeber A, Honigsmann H, Tanew A. Half-side comparison study on the efficacy of 8-methoxypsoralen bath-PUVA versus narrow-band ultraviolet B phototherapy in patients with severe chronic atopic dermatitis. Br J Dermatol. 2000;142(1):39-43.
- Diederen P, van Weelden H, Sanders C, et al. Narrowband UVB and psoralen-UVA in the treatment of early-stage mycosis fungoides: A retrospective study. J Am Acad Dermatol. 2003;48(2 Pt. 1):215-219.
- Dogra S, Mahajan R; Indian Association of Dermatologists, Venereologists and Leprologists. Phototherapy for atopic dermatitis. Indian J Dermatol Venereol Leprol. 2015;81(1):10-15.
- Duarte I, Nina BI, Gordiano MC, et al. Progressive macular hypomelanosis: An epidemiological study and therapeutic response to phototherapy. An Bras Dermatol. 2010;85(5):621-624.
- Dummer R, Ivanova K, Scheidegger EP, Burg G. Clinical and therapeutic aspects of polymorphous light eruption. Dermatology. 2003;207(1):93-95.
- Dutz J. Treatment options for localized scleroderma. Skin Therapy Lett. 2000;5(2):3-5.
- Ellis E, Scheinfeld N. Eosinophilic pustular folliculitis: A comprehensive review of treatment options. Am J Clin Dermatol. 2004;5(3):189-197.
- Elmets CA. Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2015.
- Elmets CA. Polymorphous light eruption. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2013.
- Ferrandiz C, Carrascosa JM, Just M, et al. Sequential combined therapy with thalidomide and narrow-band (TL01) UVB in the treatment of prurigo nodularis. Dermatology. 1997;195(4):359-361.
- Fesq H, Ring J, Abeck D. Management of polymorphous light eruption: Clinical course, pathogenesis, diagnosis and intervention. Am J Clin Dermatol. 2003;4(6):399-406.
- Gambichler T, Breuckmann F, Boms S, et al. Narrowband UVB phototherapy in skin conditions beyond psoriasis. J Am Acad Dermatol. 2005;52(4):660-670.
- Gathers RC, Scherschun L, Malick F. Narrowband UVB phototherapy for early-stage mycosis fungoides. J Am Acad Dermatol. 2002;47(2 Pt.1):191-197.
- George SA, Bilsland DJ, Johnson BE, Ferguson J. Narrow-band (TL-01) UVB air-conditioned phototherapy for chronic severe adult atopic dermatitis. Br J Dermatol. 1993;128(1):49-56.
- Gerstner GL. Alopecia Mucinosa. Medscape. February 14, 2017. Available at: https://emedicine.medscape.com/article/1070090-overview. Accessed January 16, 2018.
- Ghadially R, Szabo AZ, Garg A. Granuloma Annulare: Treatment & Medication. eMedicine, August 26, 2009. Available at:http://emedicine.medscape.com/article/1123031-treatment. Accessed February 15, 2011.
- Ghoreschi K, Thomas P, Penovici M, et al. PUVA-bath photochemotherapy and isotretinoin in sclerodermatous graft-versus-host disease. Eur J Dermatol. 2008;18(6):667-670.
- Gilchrest BA, Rowe JW, Brown RS, et al. Relief of uremic pruritus with ultraviolet phototherapy. N Engl J Med. 1977;297(3):136-138.
- Goldstein BG, Goldstein AO. Approach to the patient with a scalp disorder. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2017.
- Gordon PM, Diffey BL, Matthews JN, Farr PM. A randomized comparison of narrow-band TL-01 phototherapy and PUVA photochemotherapy for psoriasis. J Am Acad Dermatol. 1999;41(5 Pt 1):728-732.
- Griffiths CE, Clark CM, Chalmers RJ, et al. A systematic review of treatments for severe psoriasis. Health Technol Assess. 2000;4(40):1-125.
- Grundmann-Kollmann M, Behrens S, Podda M, et al. Phototherapy for atopic eczema with narrow-band UVB. J Am Acad Dermatol. 1999;40(6 Pt 1):995-997.
- Gupta G, Man I, Kemmett D. Hydroa vacciniforme: A clinical and follow-up study of 17 cases. J Am Acad Dermatol. 2000;42(2 Pt 1):208-213.
- Haeberle MT. Erythema annulare centrifugum. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2021.
- Hanifin JM, Cooper KD, Ho VC, et al. Guidelines of care for atopic dermatitis. J Am Acad Dermatol. 2004;50(3):391-404.
- Hawk A, English JC 3rd. Localized and systemic scleroderma. Semin Cutan Med Surg. 2001;20(1):27-37.
- Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess. 2000;4(37):1-191.
- Hodak E, Pavlovsky L. Phototherapy of mycosis fungoides. Dermatol Clin. 2015;33(4):697-702.
- Hofer A, Cerroni L, Kerl H, Wolf P. Narrowband (311-nm) UVB therapy for small plaque parapsoriasis and early-stage mycosis fungoides. Arch Dermatol. 1999;135:1377-1380.
- Hohl D. Darier disease. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2023.
- Honig B, Morison WL, Karp D. Photochemotherapy beyond psoriasis. J Am Acad Dermatol. 1994;31(5):775-790.
- Honigsmann H. UVB therapy (broadband and narrowband). UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2019; December 2021; June 2023.
- Hoppe RT, Kim YH, Horwitz S. Treatment of early stage (IA to IIA) mycosis fungoides. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2021.
- Howe W. Overview of dermatitis (eczematous dermatoses). UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2022.
- Imhof L, Ramelyte E, Dummer RG. Porokeratosis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2023.
- Ioannides D, Vakirlis E, Kemeny L, et al. European S1 guidelines on the management of lichen planus: A cooperation of the European Dermatology Forum with the European Academy of Dermatology and Venereology. J Eur Acad Dermatol Venereol. 2020;34(7):1403-1414.
- Jeanmougin M, Rain JD, Najean Y. Efficacy of photochemotherapy on severe pruritus in polycythemia vera. Ann Hematol. 1996;73(2):91-93.
- Kadin ME. Lymphomatoid papulosis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2020; December 2021; December 2022.
- Kalfa M, Koçanaogulları H, Zihni FY, et al. Therapy resistant idiopathic scleredema: An underlying pathology not always present. Eur J Rheumatol. 2015;2(4):163-164.
- Kawara S, Oiso N, Kawada A. Disseminated superficial actinic porokeratosis in a patient undergoing treatment with long-term narrowband ultraviolet B for psoriasis. J Dermatol. 2011;38(6):585-587.
- Khafagy NH, Salem SA, Ghaly EG. Comparative study of systemic psoralen and ultraviolet A and narrowband ultraviolet B in treatment of chronic urticaria. Photodermatol Photoimmunol Photomed. 2013;29(1):12-17.
- Khaled A, Kerkeni N, Baccouche D, et al. Chronic actinic dermatitis: Two patients with successful management using narrowband ultraviolet B phototherapy with systemic steroids. Therapie. 2011;66(5):453-457.
- Khan YA, Kashiwabuchi RT, Martins SA, et al. Riboflavin and ultraviolet light a therapy as an adjuvant treatment for medically refractive acanthamoeba keratitis: Report of 3 cases. Ophthalmology. 2011;118(2):324-331.
- Kim MB, Kim GW, Cho HH, et al. Narrowband UVB treatment of progressive macular hypomelanosis. J Am Acad Dermatol. 2012;66(4):598-605.
- Klecz RJ, Schwartz RA. Pruritus. Am Fam Physician. 1992;45(6):2681-2686.
- Ko MJ, Yang JY, Wu HY, et al. Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: A randomized controlled trial. Br J Dermatol. 2011;165(3):633-639.
- Kobrin SM. Uremic pruritus. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February 2020.
- Koek MB, Buskens E, Bruijnzeel-Koomen CA, Sigurdsson V. Home ultraviolet B phototherapy for psoriasis: Discrepancy between literature, guidelines, general opinions and actual use. Results of a literature review, a web search, and a questionnaire among dermatologists. Br J Dermatol. 2006;154(4):701-711.
- Koek MB, Buskens E, van Weelden H, et al. Home versus outpatient ultraviolet B phototherapy for mild to severe psoriasis: Pragmatic multicentre randomised controlled non-inferiority trial (PLUTO study). BMJ. 2009;338:b1542.
- Koreck AI, Csoma Z, Bodai L, et al. Rhinophototherapy: A new therapeutic tool for the management of allergic rhinitis. J Allergy Clin Immunol. 2005;115(3):541-547.
- Kreutz M, Karrer S, Hoffmann P, et al. Whole-body UVB irradiation during allogeneic hematopoietic cell transplantation is safe and decreases acute graft-versus-host disease. J Invest Dermatol. 2012;132(1):179-187.
- Krutmann J, Morita A. UVA1 phototherapy. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2019.
- Lau FH, Powell CE, Adonecchi G, et al. Pilot phase results of a prospective, randomized controlled trial of narrowband ultraviolet B phototherapy in hospitalized COVID-19 patients. Exp Dermatol. 2022;31(7):1109-1115.
- Lewis FM, Tatnall FM, Velangi SS, et al. British Association of Dermatologists guidelines for the management of lichen sclerosus, 2018. Br J Dermatol. 2018;178(4):839-853.
- Lowe NJ. Home ultraviolet phototherapy. Semin Dermatol. 1992;11(4):284-286.
- Marsland AM, Chalmers RJG, Hollis S, et al. Interventions for chronic palmoplantar pustulosis. Cochrane Database Syst Rev. 2006;(1):CD001433.
- McMullin MF, Bareford D, Campbell P, et al. General Haematology Task Force, British Committee for Standards in Haematology. Guidelines for the Diagnosis, Investigation and Management of Polycythaemia/Erythrocytosis. London, UK: British Society for Haematology; 2005.
- Medical Advisory Secretariat. Ultraviolet phototherapy management of moderate-to-severe plaque psoriasis. An evidence-based analysis. Ont Health Technol Assess Ser. 2009;9(27):1-66.
- Menage HD, Norris PG, Hawk JL, Graves MW. The efficacy of psoralen photochemotherapy in the treatment of aquagenic pruritus. Br J Dermatol. 1993;129(2):163-165.
- Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad Dermatol. 2010;62(1):114-135.
- Merola JF. Overview of cutaneous lupus erythematosus. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2022.
- Miguel D, Lukacs J, Illing T, Elsner P. Treatment of necrobiotic xanthogranuloma - a systematic review. J Eur Acad Dermatol Venereol. 2017;31(2):221-235.
- Millard TP, Hawk JL. Photosensitivity disorders: Cause, effect and management. Am J Clin Dermatol. 2002;3(4):239-246.
- Milstein HJ, Vonderheid EC, Van Scott EJ, Johnson WC. Home ultraviolet phototherapy of early mycosis fungoides: Preliminary observations. J Am Acad Dermatol. 1982;6(3):355-362.
- Mizuno K, Hamada T, Hashimoto T, Okamoto H. Successful treatment with narrow-band UVB therapy for a case of generalized Hailey-Hailey disease with a novel splice-site mutation in ATP2C1 gene. Dermatol Ther. 2014;27(4):233-235.
- Mohammad TF, Al-Jamal M, Hamzavi IH, et al. The Vitiligo Working Group recommendations for narrowband ultraviolet B light phototherapy treatment of vitiligo. J Am Acad Dermatol. 2017;76(5):879-888.
- Momtaz K. The benefits and risks of long-term PUVA photochemotherapy. Dermatol Clin. 1998;16(2):227-234.
- Montero LC, Belinchón I, Toledo F, Betlloch I. Progressive macular hypomelanosis, excellent response with narrow-band ultraviolet B phototherapy. Photodermatol Photoimmunol Photomed. 2011;27(3):162-163.
- Morison WL. Phototherapy and photochemotherapy for skin disease. 3rd Ed. Boca Raton, FL: CRC Press; 2005.
- Morison WL, Nesbitt JA 3rd. Oral psoralen photochemotherapy (PUVA) for pruritus associated with polycythemia vera and myelofibrosis [letter]. Am J Hematol. 1993;42(4):409-410.
- Morrell D. Hailey-Hailey disease (benign familial pemphigus). UpToDate [online serial], Waltham, MA; UpToDate; reviewed November 2014.
- Musiek A. Pityriasis lichenoides chronica. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2022.
- National Eczema Association. Prescription phototherapy. Patient Information. Novato, CA: National Eczema Association; 2023.
- Naldi L, Rzany B. Psoriasis (chronic plaque) (updated). In: BMJ Clinical Evidence. London, UK: BMJ Publishing Group; August 2007.
- Narbutt J, Torzecka JD, Sysa-Jedrzejowska A, Zalewska A. Long-term results of topical PUVA in necrobiosis lipoidica. Clin Exp Dermatol. 2006;31(1):65-67.
- National Comprehensive Cancer Network (NCCN). Primary cutaneous lymphomas. NCCN Clinical Practice Guidelines in Oncology, Version 1.2023. Plymouth Meeting, PA: NCCN; 2023.
- National Comprehensive Cancer Network (NCCN). T-cell lymphomas. NCCN Clinical Practice Guidelines in Oncology, Version 1.2022. Plymouth Meeting, PA: NCCN; 2022.
- Newland K, Marshman G. Success treatment of post-irradiation morphoea with acitretin and narrowband UVB. Australas J Dermatol. 2012;53(2):136-138.
- Olsen EA, Hodak E, Anderson T, et al. Guidelines for phototherapy of mycosis fungoides and Sezary syndrome: A consensus statement of the United States Cutaneous Lymphoma Consortium. J Am Acad Dermatol. 2016;74(1):27-58.
- Peckruhn M, Tittelbach J, Elsner P. Update: Treatment of necrobiosis lipoidica. J Dtsch Dermatol Ges. 2017;15(2):151-157.
- Petersen E, Yazdani L, Hymes SR. A case of radiation-induced bullous morphea/lichen sclerosus overlap in a breast cancer patient. Rep Pract Oncol Radiother. 2018;23(1):47-49.
- Pichon-Riviere A, Augustovski F, Garcia Marti S, et al. PUVA therapy: Main dermatology applications [summary]. IRR No. 167. Buenos Aires, Argentina: Institute for Clinical Effectiveness and Health Policy (IECS); April 2009.
- Pugashetti R, Lim HW, Koo J. Broadband UVB revisited: Is the narrowband UVB fad limiting our therapeutic options? J Dermatolog Treat. 2010;21(6):326-330.
- Raßler F, Lukacs J, Elsner P. Treatment of eosinophilic cellulitis (Wells syndrome) - a systematic review. J Eur Acad Dermatol Venereol. 2016;30(9):1465-1479.
- Resnik KS, Vonderheid EC. Home UV phototherapy of early mycosis fungoides: Long-term follow-up observations in thirty-one patients. J Am Acad Dermatol. 1993;29(1):73-77.
- Reuter J, Braun-Falco M, Termeer C, Bruckner-Tuderman L. Erythema annulare centrifugum darier. Successful therapy with topical calcitriol and 311 nm-ultraviolet B narrow band phototherapy. Hautarzt. 2007;58(2):146-148.
- Reynolds NJ, Franklin V, Gray JC, et al. Narrow-band ultraviolet B and broad-band ultraviolet A phototherapy in adult atopic eczema: A randomised controlled trial. Lancet. 2001;357(9273):2012-2016.
- Riemann H, High WA. Grover's disease (transient and persistent acantholytic dermatosis). UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2020.
- Rongioletti F. Localized lichen myxedematosus. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2019.
- Samson Yashar S, Gielczyk R, Scherschun L, Lim HW. Narrow-band ultraviolet B treatment for vitiligo, pruritus, and inflammatory dermatoses. Photodermatol Photoimmunol Photomed. 2003;19(4):164-168.
- Sapadin AN, Fleischmajer R. Treatment of scleroderma. Arch Dermatol. 2002;138(1):99-105.
- Saricaoglu H, Karadogan SK, Baskan EB, Tunali S. Narrowband UVB therapy in the treatment of lichen planus. Photodermatol Photoimmunol Photomed. 2003;19(5):265-267.
- Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis. Section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71(2):327-349.
- Sim CY, Shin JY, Lee SY, Park YL. Disseminated superficial actinic porokeratosis in a patient with psoriasis, after long-term narrowband ultraviolet B phototherapy. Ann Dermatol. 2018;30(2):211-213.
- Simon JC, Pfieger D, Schopf E. Recent advances in phototherapy. Eur J Dermatol. 2000;10(8):642-645.
- Simonsen E, Komenda P, Lerner B, et al. Treatment of uremic pruritus: A systematic review. Am J Kidney Dis. 2017;70(5):638-655.
- Snellman E. Psoriasis. In: EBM Guidelines. Evidence-Based Medicine [CD-ROM]. Helsinki, Finland: Duodecim Medical Publications Ltd.; June 18, 2004.
- Spalek M, Jonska-Gmyrek J, Gałecki J. Radiation-induced morphea - a literature review. J Eur Acad Dermatol Venereol. 2015;29(2):197-202.
- Storbeck K, Holzle E, Schurer N, et al. Narrow-band UVB (311 nm) versus conventional broad-band UVB with and without dithranol in phototherapy for psoriasis. J Am Acad Dermatol. 1993;28(2 Pt 1):227-231.
- Suh KS, Kang JS, Baek JW, et al. Efficacy of ultraviolet A1 phototherapy in recalcitrant skin diseases. Ann Dermatol. 2010;22(1):1-8.
- Sullivan TJ. Managed care’s perspective on treatment of psoriasis. Managed Care. 2003;12(5 Suppl):14-17.
- Swerlick RA. Photochemotherapy treatment of pruritus associated with polycythemia vera. J Am Acad Dermatol. 1985;13(4):675-677.
- Tan AWH, Giam YC. Lymphomatoid papulosis associated with recurrent cutaneous T-cell lymphoma. Ann Acad Med Singapore. 2004;33(1):110-112.
- Tan B, Foley P. Guttate psoriasis following Ecstasy ingestion. Australas J Dermatol. 2004;45(3):167-169.
- Tan E, Lim D, Rademaker M. Narrowband UVB phototherapy in children: A New Zealand experience. Australas J Dermatol. 2010;51(4):268-273.
- Taylor CR, Hawk JL. PUVA treatment of alopecia areata partialis, totalis and universalis: Audit of 10 years' experience at St. John's Institute of Dermatology. Br J Dermatol. 1995;133(6):914-918.
- Treister N, Li S, Lerman MA, et al. Narrow-band UVB phototherapy for management of oral chronic graft-versus-host disease. Photodermatol Photoimmunol Photomed. 2015;31(2):75-82.
- van Coevorden AM, Kamphof WG, van Sonderen E, et al. Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema: An open-label randomized controlled trial of efficacy. Arch Dermatol. 2004;140(12):1463-1466.
- Veith W, Deleo V, Silverberg N. Medical phototherapy in childhood skin diseases. Minerva Pediatr. 2011;63(4):327-333.
- Vogelsang GB, Wolff D, Altomonte V, et al. Treatment of chronic graft-versus-host disease with ultraviolet irradiation and psoralen (PUVA). Bone Marrow Transplant. 1996;17(6):1061-1067.
- Walker D, Jacobe H. Phototherapy in the age of biologics. Semin Cutan Med Surg. 2011;30(4):190-198.
- Wanat K, Rosenbach M. Necrobiosis lipoidica. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2017.
- Watsky K. Prurigo nodularis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed November 2019.
- Weberschock T, Strametz R, Lorenz M, et al. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2012;9:CD008946.
- Weibel L. Localized scleroderma (morphea) in childhood. Hautarzt. 2012;63(2):89-96.
- Weston WL, Howe W. Treatment of atopic dermatitis (eczema). UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2020.
- Whittaker SJ, Marsden JR, Spittle M, Russell Jones R. Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas. Br J Dermatol. 2003;149(6):1095-1107.
- Whitton ME, Ashcroft DM, Barrett CW, Gonzalez U. Interventions for vitiligo. Cochrane Database Syst Rev. 2006;(1):CD003263.
- Wolff D, Steiner B, Hildebrandt G, et al. Pharmaceutical and cellular strategies in prophylaxis and treatment of graft-versus-host disease. Curr Pharm Des. 2009;15(17):1974-1997.
- Wolff K. Treatment of cutaneous mastocytosis. Int Arch Allergy Immunol. 2002;127(2):156-159.
- Zanolli MD. Psoriasis and Reiter's syndrome. In: Principles and Practice of Dermatology. 2nd ed. WM Sams Jr, PJ Lynch, eds. New York, NY: Churchill Livingstone Inc.; 1996:353-354.
- Zhao M-J, Abdul-Fattah B, Qu X-Y, et al. Mycosis fungoides patient accompanied actinic keratosis, actinic keratosis with squamous cell carcinoma transformation, and porokeratosis after NBUVB therapy -- 1st case report and review of the literature. Medicine (Baltimore). 2016;95(41):e5043.
- Zheng Y, Jia J, Tian Q, et al. Lymphomatoid papulosis misdiagnosed as pityriasis lichenoides et varioliformis acuta: Two case reports and a literature review. Exp Ther Med. 2014;8(6):1927-1933.
- Ziemer M. Lichenoid drug eruption (drug-induced lichen planus). UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2021.