Treatment of primary localised cutaneous amyloidosis with cyclophosphamide

Introduction

Amyloidosis is not a single disease but rather the end result of many divergent disorders in which a characteristic fibrillar protein is deposited with in one or more tissues.[1]

In various forms of cutaeous amyloidosis, amyloid deposits occur and remain confined to the skin without involvement of internal organs.[2] When amyloid deposits occur in previously apparently normal skin, the condition is called primary localised cutaneous amyloidosis (PLCA) and when deposits occur in the skin in association with pre-existing cutaneous lesion (s), it is called secondary localised cutaneous amyloidosis.[3] Primary localised cutaneous amyloidosis can be of various types i.e. lichenoid or popular type, macular type and also can be of rare variety like nodular, bullous, vitiliginous or ichthyosiform amyloidosis. The secondary type may be due to long standing pre-exiting conditions like actinic keratosis, basal cell epithelioma, porokeratosis etc.

Treatment of PLCA is often disappointing. Topical treatment with corticosteroids with or without occlusion, 10% DMSO, retinoic acid derivatives etc. are advocated[4], but results are often unsatisfactory. Dermabrasion may be beneficial on lichen amyloidosis of the chins.[5] Etretinate appears to be helpful in relieving the pruritus in PLCA, but the condition soon relapses after the drug is stopped. A preliminary trial with long term cyclophosphamide in a dose of 50mg. daily orally showed encouraging results in lichen amyloidosis.[6]

The present study was undertaken to determine the efficacy of oral cyclophosphamide in PLCA.

Materials and Methods

The study comprised of thirty six patients of PLCA. The diagnosis was made by clinical lesions supported by biopsy if necessary. A detailed history with particular reference to duration of illness, pigmentation, itching, sizes of popular lesions and sits(s) of the lesions were recorded.

All the patients were treated with cyclophosphamide 50mg tablet daily orally. No other systemic or topical drug was prescribed for the same illness. All the patients in the reproductive age group were advised to adopt strict contraceptive measures during the period of treatment and for a few months thereafter. Patients were followed up and re-examined at the end of 1st, 3rd, and 6th months. The findings of local examination on these follow-up visits were recorded and graded on score. Any side-effect of cyclophosphamide was carefully looked for, clinically as well as by laboratory investigations. Routine examination of blood and urine, platelet count and liver function tests were carried out on each follow-up visit.

Scores made by the patients on the follow--up visits as well as the maximum size of lesions were compared with those on the initial visit and the p-value was calculated by paired - t method to know weather the clinical improvement following treatment with cyclophosphamide was significant or not.

Observation

The incidence rate of PLCA in the present study was 0.27%. Macular type of PLCA was the commonest with 13(36.11%) cases followed by biphasic type with 12(33.33%) cases and popular type with 11(30.56%). No case of nodular or other rare type of PLCA was seen. In the present series, 12(33.33%) cases were males and 24(66.67%) cases were females. The male-to-female ratio was 1:2. Female preponderance was very high in macular amyloidosis (M:F = 1:12) and it was marginally high in lichen amyloidosis (M:F= 1:2). Equal number of male and female patients presented with biphasic amyloidosis (M:F=1:1). Maximum number of cases (52.78%) were in the age group of 21-30 years. No cases of less than 10 years or more then 50 years of age was seen.

Pigmentation was the universal clinical manifestation seen in all the cases of the PLCA irrespective of clinical type. Degree of pigmentation varied from mild to instance. Pruritus of mild to severe degree was seen in all the cases of lichen amyloidosis, 11(91.57%) cases of biphasic amyloidosis and 7(53.85%) cases of macular amyloidosis. Rippled pattern of pigmentation was observed in all the cases of macular and biphasic amyloidosis. Papules arranged in such pattern of pigmentation was observed in all the cases of macular and biphasic amyloidosis. Papules arranged in such pattern were seen in 7(63.64%) cases of lichen amyloidosis. Upper back, upper limbs and lower limps were usual sites of invovement. Every patient showed involvement of one of these site alone or in various combinations. Lesions were distributed bilaterally symmetrically over these sites. Extensor aspects of limbs were more commonly involved than the flexor aspects.

Discussion

Following treatment with cyclophos-phamide 50mg tablet orally daily pruritus was the first symptom to disappear. The mean score on itching was reduced statistically (P< 0.01)after only one month of treatment. After 6 months of treatment, 92% cases showed reduction in the degree of itching, 80% to the point of no itching at all. The 2 cases who had more itching after 6 months of treatment also showed no improvement in the degree of pigmentation and size of popular lesions.

Mean score on pigmentation showed statistically significant reduction only after 6 months of treatment, (P>0.01) However pigmentation never completely disappeared in any of the treated cases. Mean size maximum of popular lesions in biphosic and lichen amyloidosis was reduced statistically significantly (P< 0.01) only after 3 months of treatment. Side effects attributable to cyclophosphamide appeared in 4(11.11%) of the 36 patients treated. Diffuse alopecia occurred in 2 patients. One of them had developed alopecia after 3 months of treatment, and it did not progress further despite continuation of treatment. Other patients had developed side effects after 6 months only. All the side-effects were reversible on stopping the treatment. Platelet count, urinalysis and liver function test were normal in all the patients during the treatment period.

From the above study we are of the opinion that various forms of PLCA can successfully be treated with cyclophosphamide.