Successful thalidomide therapy for actinic prurigo in a European woman

Actinic prurigo is a rare, often difficult‐to‐treat, idiopathic photodermatosis. Actinic prurigo is divided into a hereditary form appearing in the Native American population and a sporadic form occurring in non‐Native Americans. We present a 28‐year‐old Caucasian woman who developed typical clinical signs and symptoms of actinic prurigo, just as had her mother and grandmother. The patient and her mother were HLA‐A24 and HLA‐DR 4 with the subtype HLA‐DRB1*0408. Based on clinical symptoms and the HLA pattern, the diagnosis of actinic prurigo was made. Treatment with thalidomide led to resolution of the disease. This case report of a Caucasian woman suffering from a hereditary form of actinic prurigo questions the established classification of actinic prurigo into a hereditary Native American form and a sporadic form occurring in the non‐Native American population.     

Association of HLA subtype DRB10407 in Colombian patients with actinic prurigo

BACKGROUND: Human leukocyte antigen (HLA) DRB1*0407 had been associated with actinic prurigo in different populations. This class II HLA-DR subtype had not been studied in Colombia. OBJECTIVE: The objective of this study was to establish whether there was an association of actinic prurigo with HLA DR in a Colombian population. MATERIALS AND METHODS: Forty patients with a clinical diagnosis of actinic prurigo and 40 healthy subjects, paired by age, sex and birthplace, were studied. HLA typing for HLA DRB1 and DRB1*04, if necessary, was performed by the PCR-SSP method using blood samples. RESULTS: A high frequency of HLA DRB1*0407 was found in the patients (97.5% vs. 30%; P<0.00001). The allelic frequency of HLA DRB1*0407 was 63.8% in the case group, and 14.5% in the controls (P<0.00001). In the control group, there was a higher frequency of the alleles DRB1*01 (14.5% vs. 1.25%; P=0.0027) and DRB1*13 (23.7% vs. 2.5%; P=0.00013). LIMITATIONS: The small number of controls does not allow us to drive conclusions about other HLA alleles. CONCLUSIONS: HLA subtype DRB1*0407, found in actinic prurigo patients in studies conducted in England, Scotland, Ireland and Mexico, was also associated in Colombian patients. This finding, concordant in patients from different ethnic groups, could be helpful in the diagnosis of this disease and probably important in its pathogenesis. DRB1*01 and DRB1*13 alleles were more frequent in controls than in patients; we do not know whether they play any role in the resistance to the disease.     

Long-term thalidomide for actinic prurigo

A 35-year-old man presented at the age of 8 years with recurrent pruritic papulovesicular lesions on his face and body appearing within minutes of light exposure. A recent positive finding of human leukocyte antigen (HLA) DR4 with the rare DRB1*0407 subtype confirmed a diagnosis of actinic prurigo. Thalidomide (100 mg/day) was commenced at the age of 11 years after an unsuccessful trial of other treatments and his lesions resolved within 2 months. Attempts to withdraw thalidomide have resulted in recurrence of photosensitivity and the patient has remained on a virtually continuous maintenance dose of thalidomide (50 mg/ day) for 23 years. His cumulative dose is estimated to be over 400 g. To date, he has not experienced any adverse effects and investigations have shown no evidence of neuropathy. This case illustrates the safe long-term use of thalidomide.     

Aktinische Prurigo

The non-Native American type of actinic prurigo belongs to the group of rare idiopathic photodermatoses and therefore is often diagnosed with delay. The typical clinical and epidemiological features of actinic prurigo are described in a 10 year old girl. Detailed phototesting showed urticarial early onset and prurigo-like late onset reactions towards long-wave UVA. Repetitive photoprovocation with UVB induced delayed development of papules. HLA typing showed the typical association with HLA-DR4, in particular DRB1*0407. Treatment is usually extremely difficult and unrewarding. In this patient, the course was considerably improved by more intense physical photoprotection.     

Asociación entre HLA-DR4 y prurigo actínico: una revisión exploratoria

IntroductionDifferent studies on actinic prurigo suggest that this pathology may have an autoimmune component. Alterations have been found in peripheral blood cell subpopulations, increased lymphocytes and the expression of adhesion molecules in dermal lesions, in addition to a strong association with HLA class II.ObjectiveDescribe the current status of the association of HLA class II and actinic prurigo in the scientific literature published.Material and methodsScoping review that included PubMed, Scopus y LILACS. Empirical and theoretical publications, without a time limit written in English and Spanish were included.Result26 documents were included there are original research articles (n = 11), congress presentation (n = 1), narrative reviews (n = 6), letters to the editor (n = 4), comment (n = 1), case report (1), and case series (n = 2).ConclusionA strong association between actinic prurigo and HLA-DR4 and subtype DR4 DRB1*0407 is described. It is necessary to conduct a major number of studies for typification in other populations in order to establish the presence of unknown alleles associated with actinic prurigo. Simultaneously, it is important to increase the sample of patients with the disease and control the patient's sample to explore a possible influence of an environmental factor that modulates presence of the actinic prurigo.     

Actinic prurigo (Hutchinson''s summer prurigo)

Actinic prurigo or Hutchinson's summer prurigo is an entirely separate disease from polymorphic light eruption. The former is especially common in Mexico, Central and South America, while the latter is common in Europe. The differences between the two conditions are enumerated. It is emphasized that actinic prurigo is a chronic persistent and recalcitrant eruption which often continues throughout the winter months and affects covered as well as exposed areas of skin. A personal series of 51 patients with actinic prurigo is presented. The efficacy of thalidomide in the treatment of some cases of actinic prurigo is confirmed.     

Actinic prurigo: a retrospective analysis of 21 cases referred to an Australian photobiology clinic

Actinic prurigo (AP) is a rare acquired idiopathic photodermatosis, reported most often in American Indians, but also in Caucasian and Asian populations. The skin lesions in AP predominantly affect exposed sites but may involve covered areas, and often result in postinflammatory scarring. The diagnosis of AP can be difficult and relies on a combination of history, clinical experience and investigations including phototesting and human leucocyte antigen typing. Twenty-one patients (17 women, four men) diagnosed with AP at the photobiology clinic at St Vincent's Hospital Melbourne were reviewed in this retrospective study. The mean age of patients at presentation to the clinic was 25 years, with the mean age of onset being 14 years. Phototesting was undertaken in 20 patients, with 12 (60%) having reduced and eight (40%) normal minimal erythema doses. Human leucocyte antigen typing indicated 18 patients (85.7%) were DR4 positive, with further subtyping of the DR4 allele establishing that 15 patients (71.4%) were DRB1*0407 positive and that two (9.5%) were DRB1*0401 positive. This condition is often recalcitrant, with treatment options including photoprotection, topical and oral corticosteroids, antimalarials, phototherapy and thalidomide.     

Effectors of inflammation in actinic prurigo

BACKGROUND: Actinic prurigo is a specific familial photodermatosis of uncertain pathogenesis. OBJECTIVE: Our purpose was to investigate the immunohistologic presentation of actinic prurigo to explore the involved pathomechanisms. METHODS: The present immunohistochemical study was performed on biopsy specimens from 20 Mexican patients presenting with a severe and perennial form of the disease. RESULTS: The dense inflammatory infiltrate was composed predominantly of helper T type 1 lymphocytes admixed with scattered B-cell lymphoid follicles and numerous dermal dendrocytes. Keratinocytes contained abundant tumor necrosis factor-alpha and calprotectin. CONCLUSION: In subjects genetically predisposed to actinic prurigo, ultraviolet light may trigger excessive tumor necrosis factor-alpha production by keratinocytes whose sustained release in turn exerts its proinflammatory activity and deleterious epidermal effects. Such a cascade of events is in line with the therapeutic benefit already reported when thalidomide is used to treat actinic prurigo.     

TREATMENT OF ACTINIC PRURIGO IN CHIMILA INDIANS

Background. Actinic prurigo has a high prevalence in women of child-bearing age. Its treatment has been, among others, with thalidomide. To avoid the deleterious effects of this drug on the embryo, therapeutic alternatives have been sought. Among these, tetracycline and vitamin E have been investigated as to their influence on the symptoms of actinic prurigo. Both these drugs affect superoxide radicals that are thought to be involved in the pathogenesis of actinic prurigo. Materials and Methods. Patients (Chimila Indians with a high prevalence of actinic prurigo) received either (a) tetracycline, 500 mg three times daily, for 6 months, or (b) vitamin E, 100 IU daily, for 6 months. The patients were seen once monthly. There were eight patients in each group. Results. Both drugs used were effective. Pruritus was remarkably improved by either treatment. None of the side effects were severe enough to lead to interruption of treatment, but the observation period posttreatment was relatively short, 4 months for tetracycline and 2 months for vitamin E. The improvement occurred in spite of the continuation of extensive exposure to the sun. Conclusions. Tetracycline and vitamin E are efficacious in relieving the pruritus of actinic prurigo. Preliminary trials of a combination treatment with these two drugs is a new avenue which has shown in preliminary trials to yield synergistic effects which might allow the dosage of tetracycline to be reduced.     

Thalidomide experience of a major Australian teaching hospital

St Vincent's Hospital Melbourne cautiously prescribes thalidomide as a treatment for recalcitrant dermatoses. The guidelines used for prescribing and monitoring thalidomide for dermatological conditions at this institution are presented. Fourteen patients were treated with thalidomide (11 women, three men) over a 5‐year period. The diagnoses of patients treated were actinic prurigo, prurigo nodularis, lupus erythematosus and Behçet's syndrome. A clinical improvement was noted in 10 patients (71.4%) prescribed thalidomide. Cessation of thalidomide treatment occurred in seven patients (50%) because of adverse effects. Of the patients with adverse effects, four developed abnormal nerve conduction studies and three developed intolerable adverse events (such as dizziness and vomiting). Adverse effects from thalidomide treatment are common but, through vigilant treatment planning, patient education and regular monitoring, the risk of permanent peripheral neuropathy and teratogenicity from thalidomide toxicity can be minimized.     

Evidence that thalidomide modifies the immune response of patients suffering from actinic prurigo

BACKGROUND: Actinic prurigo (AP) is a photodermatosis with a restricted ethnic distribution, mainly affecting Mestizo women (mixed Indian and European). The lesions are polymorphic and include macules, papules, crusts, hyperpigmentation and lichenification. Thalidomide, an effective immunomodulatory drug, was first used successfully to treat AP in 1973. In this work we describe the effect that thalidomide had on TNF-alpha sera levels and on IL-4- and IFN gamma (IFNgamma)-producing lymphocytes of actinic prurigo (AP) patients. METHODS: Actinic prurigo patients were analyzed before and after thalidomide treatment. The percentage of IL-4+ or IFNgamma+ CD3+ lymphocytes was analyzed in eight of them by flow cytometry. TNFalpha in sera was measured by ELISA in 11 patients. RESULTS: A direct correlation was observed between resolution of AP lesions and an increase in IFNgamma+ CD3+ peripheral blood mononuclear cells (P < or = 0.001) and a decrease in TNFalpha serum levels (no statistical difference). No IL-4+ CD3+ cells were detected. CONCLUSIONS: Our findings confirm that AP is a disease that has an immunological component and that thalidomide clinical efficacy is exerted not only through inhibition of TNFalpha synthesis, but also through modulation of INFgamma-producing CD3+ cells. These cells could be used as clinical markers for recovery.     

Thalidomide and its dermatologic uses

Thalidomide is a beneficial agent for treating a variety of refractory dermatologic disorders including erythema nodosom leprosum, lupus erythematosus, prurigo nodularis, actinic prurigo, pyoderma gangrenosum and aphthous stomatitis. Two thalidomide analogues, lenalidomide and CC-4047, are considerably more potent with decreased side effects when compared to thalidomide. They are currently undergoing trials and show promise, as they have increased immunomodulatory and anti-angiogenic activity. This category of medication and its use will be reviewed.     

Treatment of actinic prurigo with intermittent short-course topical 0.05% clobetasol 17-propionate. A preliminary report

Actinic prurigo is a chronic familial photodermatosis that occurs mostly in Amerindians. Eight patients with actinic prurigo were given intermittent 3- to 14-day courses of topical 0.05% clobetasol 17-propionate cream or ointment in 1988 and 1989. Seven out of eight patients cleared or markedly improved. All of the patients had been resistant previously to milder topical corticosteroids. There have been no side effects. This therapy offers an effective alternative to systemic corticosteroids, oral psoralen with long-wave UV radiation in the A range, or thalidomide.     

Lymphocyte subtypes and adhesion molecules in actinic prurigo: observations with cyclosporin A

BACKGROUND: Actinic prurigo is a photodermatitis in which UV light is implicated by an unknown mechanism. METHODS: Skin biopsies of 19 patients with actinic prurigo and 11 controls were analyzed by immunohistochemistry. RESULTS: In actinic prurigo patients, there was a significant increase in the number of CD3, CD4, CD8, CD45RA, CD45RO, and CD45RB lymphocytes and Langerhans cells, as well as in the level of human leukocyte antigen-DR (HLA-DR) expression and cell adhesion molecules lymphocyte functional antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Actinic prurigo patients were treated with cyclosporin A (CsA), and a final skin biopsy was taken after 6 months of treatment. All the cell populations and markers studied, except for the CD4 lymphocytes, Langerhans cells, and HLA-DR expression, returned to normal levels. CONCLUSIONS: CsA was found to be effective in relieving the clinical symptoms of actinic prurigo.     

Case for diagnosis. Actinic prurigo

A 13-year-old black boy had pruritic papular and nodular lesions on his forearms associated to edema of the lower lip, photophobia, conjunctivitis and pterygium. Skin biopsy of the lower lip revealed acanthosis, spongiosis with dermal perivascular mononuclear cell infiltration composed by lymphocytes, plasma cells and eosinophils consistent with actinic prurigo. Lesions improved considerably with the use of thalidomide 100mg/ day.     

A case of actinic prurigo showing hypersensitivity of skin fibroblasts to ultraviolet A (UVA)

We here report a patient with actinic prurigo. He had had erythematous papulovesicular eruptions on the sun-exposed sites from fall to early summer for 4 years. The lesions healed leaving atrophic scars. The histology showed epidermal necrosis and dermal dense perivascular lymphohistiocytic infiltration and edema. His minimal erythema doses to ultraviolet B (UVB) and UVA were normal and lowered, respectively. Skin lesions were produced by repeated irradiation with UVA plus UVB, but not with UVA alone. Then he was diagnosed as having actinic prurigo. Skin fibroblasts from the patient were hypersensitive to UVA. We believe that the hypersensitivity relates to the pathomechanisms of the photosensitivity in the case. UVA sensitivity of fibroblasts may be useful for differentiating actinic prurigo, hydroa vacciniforme, and other similar photosensitive disorders.     

HLA typing in polymorphous light eruption

Human leukocyte antigen typing of 41 white patients with polymorphous light eruption (limited concept) showed no significant differences when compared with the typing of 51 white control subjects. We previously found that actinic prurigo, an idiopathic photodermatosis particularly associated with Amerindians, has a positive association with antigens A24 and Cw4 and a negative association with A3. We suggest, on the basis of both laboratory and clinical findings, that polymorphous light eruption (limited concept) and actinic prurigo are two different and distinct diseases.     

Actinic prurigo, tropical (South-East Asian) variant.

Actinic prurigo is a chronic familial photodermatitis found predominantly among the Amerindians. It has been reported from North and South America, Britain and Japan. We report a case of actinic prurigo seen in Singapore. A 20-year-old Malay female presented with a persistent pruriginous eruption in the sun-exposed parts and on her abdomen. She also had lower lip cheilitis and thinning of the outer eyebrows, features often seen in actinic prurigo. The minimal erythema dose to ultraviolet A (UVA) and UVB were persistently lowered. We propose that this condition be called actinic prurigo, tropical (South-East Asian) variant.