Lack of effect of cyclosporine in lichen amyloidosis associated with atopic dermatitis

ARTICLE

Several skin diseases are associated with cutaneous amyloidosis, including atopic dermatitis [1-3], lichen planus [4], mycosis fungoides [5], and disseminated superficial porokeratosis [6]. Chronic scratching [7], viral [8] and genetic factors [9] seem to be the causes. However, the precise pathogenesis of lichen amyloidosis is unknown.

Different treatment modalities have been advocated with variable responses. However, treatment of lichen amyloidosis is extremely difficult, and not always successful. Behr et al. [1] is the only one to report the benefit of cyclosporine for lichen amyloidosis.

We report a case of lichen amyloidosis associated with atopic dermatitis, which was unresponsive to cyclosporine.

Case report

A 20-year-old white man with history of atopic dermatitis presented pruritic pigmented eruptions affecting mainly the extensor surfaces of the arms, and sacral and interscapular areas. He had a medical history of using various topical and systemic steroids, and antihistamines. His aunt also had a history of atopic dermatitis. His father had allergic rhinitis.

Examination revealed erythematous, lichenified and crusted papules on the upper aspect of the back, chest, sacral area, face and the extensor surfaces of upper arms. Usually symmetrically distributed, small dusky brown or grayish pigmented, pruritic, multiple and discrete hyperkeratotic papules were especially seen on the extensor surfaces of upper arms, sacral area and upper aspect of the back
(Figs. 1 and 2). The patient stated that he had these lesions for about 6 years, and had not undergone remission since they first appeared. In addition, he had xerosis, scaling, positive white dermographism, facial erythema and Dennie-Morgan folds.

Punch biopsies were obtained from papules on the extensor surface of his right upper arm and the upper aspect of back before and after treatment.

Histopathological examination revealed hyperkeratosis, irregular acanthosis, and scattered necrotic keratinocytes on the basal layer of the epidermis. In the papillary dermis, pigment incontinence and eosinophilic globular material were seen (Fig. 3). This material was stained positively with Congo red, and demonstrated apple-green birefringence when viewed under polarized light.

Serum IgE was 194 IU/ml (normal level < 100 IU/ml) and eosinophil count was 475. All other investigations (complete blood count, biochemical profile, plasma protein electrophoresis, rheumatoid factor, antinuclear factor, creatinine clearance, urine protein extraction and examination for Bence-Jones protein, parathyroid hormone, thyroid hormones, thyrotropin, vanillyl mandelic acid, adrenaline, noradrenaline, chest X-ray, abdominal ultrasound, electrocardiography, echocardiography) were normal or negative. There was no evidence of systemic amyloidosis.

Oral cyclosporine was given 5 mg/kg daily and the patient evaluated every month. At the end of 3 months of therapy, the drug was discontinued because clinical and histological improvement were not achieved. Also four months after stopping therapy no clinical and histological resolution was noted. After this period PUVA treatment was tried for 3 months, but no improvement was seen.

Discussion

Lichen amyloidosis is a papular, intensely pruritic type of amyloydosis of unknown cause. It is known that amyloid in lichen amyloidosis is not derived from immunoglobulins or serum proteins, as it is in systemic amyloidoses, but from keratin peptides of necrotic keratinocytes. Necrosis and/or apoptosis of keratinocytes may be induced by prolonged scratching, as may be epithelial hyperplasia, hypergranulosis, and compact orthokeratosis. Scratching seems to be the first and single most important step in the development of lichen amyloidosis [3].

Lesions in lichen amyloidosis are found mainly on the anterior legs, but can occur on the back, forearm and thighs. The deposits are usually confined to the papillary dermis and do not involve blood vessels or adnexal structures. In addition, there is irregular acanthosis and hyperkeratosis of the overlying epidermis [10].

A number of treatments for lichen amyloidosis have been described and but the results are frequently unsatisfactory. Therapeutic options include topical and intralesional corticosteroids, dermabrasion, scalpel scraping, etretinate, calcipotriene, topical dimethyl sulfoxide, UV-B therapy, and cyclophosphamide [1].

Behr et al. [1] tried oral cyclosporine 4 mg/kg daily in a patient with lichen amyloidosis associated with atopic dermatitis. The patient noted a decrease in pruritus approximately 2 weeks after beginning this therapy. One month later, the atopic dermatitis remitted completely, and the number and size of the lichen amyloidosis lesions were dramatically reduced. During a 7-month course, the cyclosporine dose was tapered 100 mg/day, with no recurrence of skin eruption. Nine months after cyclosporine therapy, his atopic dermatitis remained in remission. The lichen amyloidosis papules had flattened completely and remained asymptomatic. The result of histopathological examination demonstrated improvement in acanthosis and hyperkeratosis, with persistence of amyloid deposits in the papillary dermis in a biopsy specimen taken after 2 months of cyclosporine therapy.

Cyclosporine affects various intracellular signal transduction pathways. Through these pathways, cyclosporine modulates the production of key inflammatory proteins, thereby suppressing immunological responsiveness [11]. Cyclosporine may also suppress the production of cytokines that cause pruritus [12]. Behr et al. [1] suggested that cyclosporine may act directly to attenuate the pruritic symptoms of lichen amyloidosis and/or modulate un-known immune mediators contributing to the formation of amyloid fibrils.

Clinical improvement in our case was not seen during a 3-month therapy. Papular lesions showed no flattening; furthermore, his itching increased. No histological change was seen in a biopsy taken at the end of therapy. Although cyclosporine is nephrotoxic and hypertensive, we could not seen any adverse reactions during treatment. Also four months after stopping therapy no clinical and histological resolution with cyclosporine was noted.

We thought that a three-month treatment was enough to exclude improvement, because of the fact that Behr et al. [1] noted a decrease in pruritus approximately 2 weeks, and a reduced number and size of the lichen amyloidosis lesions one month later after beginning therapy. It might be possible that the lack of effectiveness of cyclosporine in our patient is due to the absence of acute eczematous attack of atopic dermatitis. In conclusion, oral cyclosporine was not found to be effective in the treatment of lichen amyloidosis associated with atopic dermatitis in this case. To evaluate the effectiveness of cyclosporine in lichen amyloidosis with atopic dermatitis, it will be necessary to study a larger group of patients.

Article accepted on 3/9/02

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