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

Australasian Journal of Dermatology (2002) 43, 128 132 CASE SERIES Actinic prurigo: A retrospective analysis of 21 cases referred to an Australian photobiology clinic Rohan Crouch, 1 Peter Foley 1,2 and Christopher Baker 2 1 The University of Melbourne, Department of Medicine (Dermatology) and 2 Department of Dermatology, St Vincent s Hospital Melbourne, Melbourne, Victoria, Australia SUMMARY 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. Key words: cheilitis, human leucocyte antigen, photosensitivity disorders, phototesting, sunlight, thalidomide. INTRODUCTION Actinic prurigo (AP) is an acquired idiopathic photodermatosis characterized by an intensely pruritic, excoriated, papular or nodular eruption that frequently results in postinflammatory scarring. 1 The condition is seen primarily in American Indians, with reports originating from Central, North and South America. 2,3 It is reported less frequently in Caucasian 4 6 and Asian populations. 7 Although exposed sites are most frequently affected (including the dorsum of the hands and forearms, V of the chest, face, ears, legs and feet), covered sites, particularly the buttocks, may be involved. Cheilitis, particularly involving the lower lip, and conjunctivitis are often reported. 1,6 Actinic prurigo is more common in women, with onset most often in childhood 8 but also reported in adulthood. 6,9 The condition has a chronic time-course, although seasonal variation may be present, with exacerbation in the spring and summer months. 1 The aetiology is unknown, with hereditary factors considered important. 4,10,11 A recent study suggested AP and polymorphic light eruption possess a common genetic background, 12 despite the conditions being clinically distinct. Light testing has variable success in establishing the action spectrum of AP patients, with the majority of patients sensitive to either or both of ultraviolet A (UVA) and ultraviolet B (UVB). 13 Actinic prurigo has been rarely reported in Australia. 14,15 We present a retrospective analysis of patients diagnosed with AP attending the photobiology clinic at St Vincent s Hospital Melbourne between 1993 and 2001. METHODS Correspondence: Dr Peter Foley, The University of Melbourne, Department of Medicine (Dermatology), St Vincent s Hospital Melbourne, PO Box 2900, Fitzroy, Vic. 3065, Australia. Email: foleyp@svhm.org.au Rohan Crouch, MB BS. Peter Foley, FACD. Christopher Baker, FACD. Submitted 20 September 2001; accepted 20 December 2001. All patients attending the photobiology clinic at St Vincent s Hospital Melbourne from April 1993 to August 2001 for evaluation of suspected photosensitivity were entered onto a prospective database established using Microsoft Access (Version 7). Those patients recorded in the database with a diagnosis of AP were included in this retrospective study. The diagnosis of AP was based on typical history, clinical features, phototest results and human leukocyte antigen (HLA) typing, as described in the introduction. Investigations included

Actinic prurigo 129 phototesting and pathological studies such as porphyrin screening, HLA typing, antinuclear factor, extractable nuclear antigen and anti-doublestranded DNA. Monochromator light testing and broadband light testing to UVA/UVB was conducted as previously described. 15 Phototesting was judged as normal or abnormal by a dermatologist. Patients did not have their lesions biopsied as part of their diagnostic workup. RESULTS A total of 21 patients diagnosed with AP were seen. There were 17 women (81%) and four men (19%). The mean age of AP patients referred to the clinic was 25 years (range 4.5 64.9 years), with the mean age of onset 14 years (range 2 43 years). The forearms were the most frequently involved site. Human leucocyte antigen typing was conducted in all patients with 18 (85.7%) DR4 positive (Table 1). All patients screened for antinuclear factor, extractable nuclear antigen, anti-doublestranded DNA and porphyrins had negative or normal results. Of the six patients with a family history of AP, three were from one family, and two from another. Phototesting was conducted in 20 patients (95.2%), with 12 (60%) having reduced minimal erythema doses (MED) (Fig. 1). All patients reported successful reduction in cutaneous disease by using sunlight-avoidance techniques such as minimizing outdoor activities and wearing appropriately protective clothing. Sunscreens were of limited use in all cases, with no patients reporting this to be an effective treatment. The majority of patients had used antihistamines (e.g. fexofenadine, loratadine) with little or no effect. Oral prednisolone (dose range 12.5 25 mg/day) was used by 11 patients and reported by all to be beneficial in controlling acute exacerbations. In one patient, oral prednisolone (25 mg/day) reduced the extent of the rash during the summer months but clearing did not occur. Topical corticosteroids (including betamethasone dipropionate, mometasone furoate and hydrocortisone) were beneficial as a treatment in reducing itch and inflammation of lesions once present. However, they were not used as prophylactic measures. Antibacterial agents (topical and oral) were prescribed in patients following infection of excoriations, with no patient receiving oral antibiotics reporting them to be beneficial in preventing lesions. Antimalarials were ineffective in three patients (hydroxychloroquine sulfate, dose range 200 400 mg for 3 6 months) with only one other reporting that hydroxychloroquine sulfate (200 mg twice daily) for 3 months during summer resulted in a marked reduction of the rash with no side-effects. -carotene (20 mg twice daily) was prescribed prior to attending the clinic in three patients, with one patient reporting limited success and the others having no improvement following a 3-month course. Cimetidine (600 mg/day) successfully controlled one patient s pruritus without changing his photosensitivity or the clinical appearance of his skin. Ultraviolet phototherapy was used with some success. Broadband UVB during spring and early summer was used in the clinic for one patient who, after receiving eight treatments to a total cumulative dose of 750 s (approximately 15 MED) reported it as useful in preventing new lesions. Narrowband UVB therapy in two patients (48 treatments, cumulative dose 42.1 J/cm 2, and 11 treatments, cumulative dose 2.7 J/cm 2 ) and psoralen and UVA (PUVA) therapy in another patient (details unavailable) was used outside the clinic and were also reported by patients to be useful. However, the benefit of ultraviolet phototherapy was temporary, with the achieved artificial hardening diminishing throughout the winter months unless phototherapy was continued. Thalidomide was prescribed in the spring and summer months in six patients (dose range 50 100 mg/day for 1 6 months), 16 with patients using topical corticosteroids concurrently as required. The starting dose of thalidomide in Table 1 Features of patients with actinic prurigo (n = 21) Feature No. (%) Referral by a dermatologist 19 (90.5) Family history of actinic prurigo 6 (28.6) High resolution typing of DR4 allele DRB1*0407 15 (71.4) DRB1*0401 2 (9.5) Personal history of atopy 7 (33.3) Hypopigmentation 20 (95.2) Site of lesions Forearms 20 (95.2) Legs 17 (81) Face 14 (66.7) Hands 8 (38.1) Neck 6 (28.6) Lips (actinic cheilitis) 5 (23.8) Ears 4 (19.0) Conjunctiva 0 ( Figure 1 Phototest results in actinic prurigo patients (n = 20)., Combined UVA/UVB sensitivity 20%;, UVA sensitivity alone 40%;, Normal 40%.

130 R Crouch et al. most patients was 100 mg/day, with reduction to a maintenance dose of 50 mg/day or 50 mg every second day if possible. One patient developed urticaria within days of commencing treatment. Significant clinical improvement was reported in the other five following a 1 3 month course, with a reduction in skin lesions during the summer months. One patient was treated successfully without side-effects and remained free of symptoms following cessation as previously described. 15 In two patients, thalidomide resulted in significant improvement of their condition during the summer months without side-effects. These two patients do not require thalidomide treatment during the winter months and are treated on a seasonal basis. Three AP patients ceased thalidomide due to side-effects, the one mentioned above who developed urticaria days following treatment initiation, and two due to development of nerve conduction changes considered abnormal. DISCUSSION Actinic prurigo is a so-called idiopathic, probably immunologically based photodermatosis. The relevance of atopy in AP is unknown, however, a personal or family atopic history is often reported. 5,13 In our patients, the frequency of atopy was no higher than that found in the Victorian population. 17 Cheilitis was not a common feature in our patients compared with previous data. 5,13 Postinflammatory scarring and hypopigmentation were evident in almost all patients, higher than reported in other populations. 13 A family history of AP was reported less often in our population compared with American Indians, 9 but this may be due to a lack of awareness in the local population. Recent findings have increased interest in major histocompatibility studies in American Indian and Caucasian populations. An initial HLA association was reported in American Indians with AP where an increased frequency of the Cw4 and A24 antigens was found. 18 Since then, HLA typing undertaken on 26 British Caucasian AP patients has found that all 26 patients were DR4 positive, with further subtyping establishing that 60% of these patients carried HLA DRB1*0407, compared to none of 20 controls (P = 0.002). 4 A subsequent study in Mexico found a significantly higher incidence of DR4 in AP patients (93%) compared to controls (57%), with many of these patients carrying DRB1*0407. 10 More recently, eight out of eight French patients HLA-tested carried DRB1*0407. 5 The general population carriage of DR4 in Australia is approximately 30%, 19 with carriage of DRB1*0407 estimated at between 4 and 8% of DR4 positives. 4,12 Similar to previous findings, 4,11 our AP population has an increased incidence of DR4, and in particular DRB1*0407, compared with the general population. High-resolution HLA typing should be performed for DRB1*0407 as, although not diagnostic, this may aid in establishing a diagnosis. Phototesting in AP yields variable results, with an action spectrum involving UVA, UVB or a combination of these. In a previous study of 53 British AP patients undergoing light testing, 40 (75.5%) were reported as abnormal, with 17 patients having an abnormal action spectrum in the UVB range alone, five in the UVA range alone and 18 in the combined UVA/UVB range. 13 This is consistent with our experience in which 60% of patients tested had abnormal phototest results. All 12 of our patients with reduced MED had action spectra incorporating UVA. Replication of lesions was not attempted as a regular part of our investigations. Patients were encouraged to attend the clinic during acute exacerbations if there was any doubt concerning the diagnosis and if biopsies were required. The biopsy results are considered not diagnostically specific in AP 20 and were rarely considered necessary in the photobiology clinic where a combination of clinical experience, phototesting and HLA typing was used to make the diagnosis. Phototesting is valuable in determining the action spectrum of individual patients and subsequently may be beneficial in planning treatment strategies (e.g. phototherapy). Actinic prurigo is a recalcitrant condition and treatments must be individually tailored. Treatment options used by our Table 2 Treatment options in actinic prurigo Treatment St Vincent s Hospital Melbourne experience Literature Sun avoidance Helpful in all cases as a prophylactic measure. Helpful but impractical. 1,21 Sunscreens Ineffective Generally provide little relief. 1,2 Topical corticosteroids Marginal help in reducing itch and inflammation High potency agents useful in clearing lesions of active lesions. but not prophylactic. 22,23 Systemic corticosteroids Control of acute exacerbations in 11/11. As a Often helpful in acute exacerbations. 23 prophylactic measure, reduced extent of rash in 1/1 (not clear). Antibiotics Treatment of secondary infection, no benefit in Treatment of secondary infection only. 21 preventing new lesions. Antimalarials As a prophylactic measure, ineffective 3/4, marked Little benefit. 5 reduction 1/4. -carotene As a prophylactic measure, unhelpful 2/3, limited Limited benefit. 21,24 benefit 1/3. Phototherapy As a prophylactic measure, helpful in 4/4. Usually helpful. 24 26 Thalidomide Rapid reduction in activity of acute lesions. Reduction Very effective. 3,14 16,27,28 in new skin lesion number and severity. Cimetidine Reduced pruritus 1/1. No previous report. Oral antihistamines Little or no effect. Helpful in eczematous phase but no long-term benefit. 21

Actinic prurigo 131 unit and those reported in the literature are summarized in Table 2. The majority of our patients had summer exacerbations, with winter eruptions also reported. Seasonal treatment beginning in the spring and continuing throughout the summer months was commonplace, while in a smaller proportion of cases the rash persisted throughout winter and treatment was undertaken continuously. Australian patients perhaps do not show as marked seasonal variation as those from less sunny climates. Restriction of sun exposure is ultimately the best treatment, but is not a realistic option for most patients. The use of broad-spectrum sunscreens (SPF 30 + ) can be beneficial in mild cases but generally provides little relief. Oral corticosteroids are beneficial in providing temporary relief during acute exacerbations, but do not result in clearing of prurigo lesions. Although potent topical corticosteroids have been reported to be beneficial in some patients, 22 in our experience patients only received marginal benefit from the topical corticosteroids currently available in Australia. While regular application to developed lesions appeared to hasten resolution, new lesions continued to appear. Antimalarial treatments have been attempted with little success in reduction of photosensitivity. 5 In our experience, the use of antimalarial drugs on a seasonal basis combined with monitoring for adverse effects was considered for recalcitrant cases, but was rarely of much clinical benefit. The prescription of -carotene as a photoprotective agent has also had limited success. 21,24 The use in low doses compared with previous reports 21,24 may account for its lack of success as a photoprotective agent in this series. As cimetidine is an H 2-receptor antagonist it is likely that the success in the one patient where it was used is related to a reduction in pruritus through H 2 blockade or an immunomodulatory action. It is considered unlikely that cimetidine acted to reduce photosensitivity but, given its success in decreasing pruritus, it should be considered as a treatment option. The use of PUVA with a mean cumulative dose of 58 J/cm 2 has been reported to successfully treat five women (aged 30 39 years) in which other treatment regimes, excluding thalidomide, had little benefit. 25 Narrowband UVB has been used successfully, with patients reporting this form of phototherapy to be as effective as previous PUVA therapy. 26 In our series, seasonal ultraviolet treatment was attempted, with increased sun tolerance and reduction of skin lesions using narrowband UVB, PUVA and broadband UVB therapy. All patients benefiting from phototherapy had normal MED on phototesting and clinical photosensitivity returned without maintenance phototherapy during the winter months. High-dose thalidomide (300 mg/day) was first reported to give dramatic clinical improvement in American Indians with AP. 3 Thalidomide treatment has now been widely used for AP, 27,28 with one patient successfully controlled for 23 years. 14 In our experience, low-dose thalidomide (dose 50 100 mg) is very successful in controlling AP, but treatment can be complicated by adverse side-effects, which culminate in its withdrawal. 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