Amyloidosis Cutis Dyschromica: A Rare Reticulate Pigmentary Dermatosis.

We are reporting a rare case of amyloidosis cutis dyschromica in a 41-year-old man. This is a rare form of primary cutaneous amyloidosis characterized by reticulate pigmentation with hypopigmented and hyperpigmented macules, onset in childhood, familial tendency in some, occasional mild itching and deposition of amyloid in the papillary dermis. Our case also had multiple bilaterally symmetrical hyperpigmented keratotic papules abutting the axillary vault resembling those seen in Dowling-Deogs disease. The other unusual feature in this patient was the strong family history of vitiligo, which we are unable to explain. We have also tried to explain the mechanism leading to the hyperpigmentation and hypopigmentation in amyloidosis cutis dyschromica.

What was known?

Amyloidosis cutis dyschromica (ACD) is a rare form of primary cutaneous amyloidosis and is characterized by reticulate hyperpigmentation interspersed with hypo and depigmented macules diffusely spread all over the body, with occasionally associated mild itch, onset before puberty and deposition of amyloid immediately below the epidermis.

It can look similar to dyschromatosis universalis hereditaria, generalized Dowling–Degos disease, xeroderma pigmentosum and poikilodermatous amyloidosis.

Genetic factors have been implicated. UVB- and UVC-induced damage to keratinocytes is said to take a longer time for repair in ACD. The destroyed keratinocytes due to delayed DNA repair undergo apoptosis. The cytokeratin of the apoptotic keratinocyte is phagocytosed by histiocytes and fibroblasts and that is responsible for the amyloid formation.

There is no uniformly successful treatment modality of ACD and there are anecdotal reports of success with acitretin, CO2 laser, keratolytics, topical steroids, etc.

Introduction

A rare case of amyloidosis cutis dyschromica (ACD) is being described in a middle-aged Muslim man who had a strong family history of vitiligo. His patchy dyschromic lesions started from the age of 6 years and gradually increased to involve practically the whole trunk and all extremities but spared the face, palms and soles. Individually they were hyperpigmented macules and few keratotic papules interspersed with very sharply marginated hypo and depigmented macules. Such a clinical picture prompts a dermatologist to think of Dowling–Degos disease, dyschromia universalis hereditaria, xeroderma pigmentosum (XP) and the rare ACD or poikilodermatous cutaneous amyloidosis. A skin biopsy revealed amyloid pigment in the papillary dermis confirming the diagnosis of ACD. ACD is a rare form of primary cutaneous amyloidosis which is refractory to all forms of treatment with only anecdotal reports of treatment modalities like acitretin, topical steroids, keratolytics and CO2 lasers.

Case Report

A 41-year-old Muslim man living in South Africa presented to this clinic with diffuse patchy dyschromic lesions on the body. He was born of a consanguineous marriage between second-degree relatives. He said he started developing gradually increasing diffuse hyperpigmentation starting from his trunk followed by patchy hypopigmentation and depigmentation from the age of 6 years all over the body. He had recently noticed a few hypopigmented macules on his forehead and balding scalp. Cutaneous examination revealed diffuse reticulate pigmentation of the entire body sparing palms, soles, dorsa of hands, feet and face and an island in the presternal area which he said was his original color. The hypopigmented macules were variably sized, well defined and ranged from tiny 4 mm to about 2 cm in diameter [Figure 1a and b]. Some scattered hyperpigmented keratotic papules were found on the extremities and proximal inner arms abutting the axillae, which had been growing for the past 4 years [Figure 2a and b]. All lesions were asymptomatic with no blistering, ulceration, atrophy, poikilodermatous changes, scaling or oozing. Palms, soles, mucosae, hairs and nails were normal. The patient gave no history of photosensitivity, any systemic abnormality or any inflammatory dermatosis and there was no growth retardation. The possibility of dyschromatosis universalis hereditaria, generalized Dowling–Degos disease and xeroderma pigmentation were kept in mind. A 3-mm punch biopsy revealed amorphous pink masses of amyloid in the papillary dermis [Figure 3]. Based on clinicopathological correlation, a diagnosis of ACD was made.

Figure 1

(a) Reticular pigmentation of the anterior trunk with patchy hypopigmented and depigmented macules. (b) Reticular pigmentation of the posterior trunk with patchy hypopigmented and depigmented macules

Figure 2

(a) Keratotic papules in the most proximal part of right arm with multiple hyperpigmented keratotic papules. (b) Keratotic papules in the most proximal part of left arm with multiple hyperpigmented keratotic papules

Figure 3

Congo red staining showing pinkish amorphous amyloid deposited in the papillary dermis

Discussion

ACD is a rare variant of primary cutaneous amyloidosis. On evaluating data as recently as November 2012, less than 40 cases have been reported in the world literature so far.[12] Reports have been predominantly from South East Asian countries.[13] ACD is characterized by a typical reticulate hyperpigmentation interspersed with hypo and depigmented macules diffusely spread all over the body, occasional reports of associated mild itch, onset before puberty and deposition of amyloid immediately below the epidermis.[123] Scattered hyperpigmented keratotic papules that interspersed within the dyschromic lesions which when biopsied also showed deposition of amyloid have been reported.[1234] Freckles, telangiectasias, atrophy in the lesions and blisters have been reported rarely.[156] Poikilodermatous and bullous variants of ACD have also been documented.[1] Concomitant connective tissue disorders like systemic sclerosis, systemic lupus erythematosus and dermatomyositis and generalized morphoea as well as atypical Parkinsonism with motor weakness and spasticity with no systemic amyloidosis and colon carcinoma have been reported in the literature too.[12]

The etiology of ACD does not seem very clear. Genetic factors have been implicated owing to the fact that it occurs before puberty and shows a familial predilection.[127] UVB- and UVC-induced damage to keratinocytes is said to take a longer time for repair in ACD.[18] The destroyed keratinocytes due to delayed DNA repair undergo apoptosis. The cytokeratin following keratinocyte apoptosis is phagocytosed by histiocytes and fibroblasts and that is responsible for the amyloid formation.[4] The amyloid is said to be derived from keratinocytes with positive cytokeratin staining. However, the point against photoexposure is that sun-exposed areas in ACD often show milder presentation compared to the trunk.[1] Existing literature does not clearly explain the mechanism for dyschromia. Hypopigmentation and hyperpigmentation is a novel finding in ACD unlike what is seen in the other common variants of primary cutaneous amyloidosis like macular amyloidosis or lichen amyloidosis where only hyperpigmentation is a feature. A hypothesis for consideration would be that the dyschromia occurs in ACD due to two factors, i.e., the balance between epidermal pigment retention and dermal pigment deposition. Any damage will result in some amount of melanin sequestration within superficial dermal melanophages. When epidermal melanin remains normal or increase the underlying melanophages, it will contribute to clinical hyperpigmentation. On the other hand, when epidermal melanin is drastically reduced due to decreased pigment donation to keratinocytes from the melanocyte, or due to damage to the melanocytes, clinical hypopigmentation can occur. Since the deposits are in the papillary dermis they may stretch the basement membrane, thereby the basal cell layer reducing the density of melanocytes per mm resulting in hypo/depigmentation in that area.

This rarely encountered entity can be mistaken for dyschromatosis universalis hereditaria, generalized Dowling–Degos disease, XP and poikilodermatous amyloidosis.[1234] The amyloid deposition in papillary dermis and the absence of other histological features are easy to make the histological diagnosis of ACD. Additionally, ACD lacks the marked photosensitivity, very premature actinic damage and the associated cutaneous malignancies seen in XP.[2] Though poikilodermatous amyloidosis can cause histological confusion with ACD, the former presents with lichenoid papules, early blistering of extremities, photosensitivity, short stature and palmoplantar keratoderma in addition to poikiloderma.[2]

ACD is known to be refractory to most forms of therapy despite scattered anectodal reports of efficacy of topical steroids, keratolytics, capsaicin, dimethyl sulfoxide and CO2 laser.[123456] Literature has shown variable efficacy of oral acitretin owing to its ability to induce apoptosis, thereby reducing the available keratinocytes, the most probable source of amyloid. Acetretin probably aids phagocytosis by macrophages, thereby ridding the dermis of amyloid.[2] Photoprotection is strongly recommended in all cases. Our patient avoids sun exposure and uses broad spectrum sunscreens but has refused any active topical or systemic medication. It is not possible to explain the association of ACD with such a strong family history of vitiligo in this patient except for the fact that genetic factors, consanguinity and involvement of melanocytes are evident in both these entities.

Learning points

We have tried to hypothesize as to the mechanism of concurrent hypopigmentation and hyperpigmentation in ACD, which no other case report on this entity has done to the best of our knowledge

Keratotic hyperpigmented papules though not common can be seen in this entity where the predominant and pathognomonic lesions are diffusely scattered hypopigmented and hyperpigmented macules. Presence of such papules in areas like proximity of the axillary vault can confuse the clinician because it is reminiscent of Dowling–Degos disease where hypo and hyperpigmented macules both are being increasingly documented in Indian patients with Fitzpatrick phototype IV and V skin

Our patient of ACD had a strong family history of vitiligo. This observation may be noteworthy for future cases to further probe any remote association between the two.

What is new?

We have tried to hypothesize as to the mechanism of concurrent hypopigmentation and hyperpigmentation in ACD, which no other case report on this entity has done to the best of our knowledge

Keratotic hyperpigmented papules though not common can be seen in this entity where the predominant and pathognomonic lesions are diffusely scattered hypopigmented and hyperpigmented macules. Presence of such papules in areas like proximity of the axillary vault can confuse the clinician because it is reminiscent of Dowling–Degos disease where hypo and hyperpigmented macules both are being increasingly documented in Indian patients with Fitzpatrick phototype IV and V skin

Our patient of ACD had a strong family history of vitiligo. This observation may be noteworthy for future cases to further probe any remote association between the two.