Macular amyloidosis represents a common variant of primary localized cutaneous amyloidosis, the later being characterized by deposition of a proteinaceous substance composed of one of a family of biochemically unrelated proteins in previously apparently normal skin. Lichen planus is an interface dermatitis where apoptotic keratinocytes may be present in the dermis. Here we describe a patient with macular amyloidosis associated with chronic lichen planus. The case is being reported because of rarity of the association.
Amyloidosis is a generic term that signifies the abnormal extracellular tissue deposition of one of a family of biochemically unrelated proteins that share certain characteristic staining properties, including apple-green birefringence of congored stained preparations viewed under polarising light. Clinically macular amyloidosis presents as poorly delineated hyperpigmented patches of grayish-brown macules with a rippled pattern, associated with deposition of amyloid material in the papillary dermis. The close proximity of the amyloid deposits to the lower epidermis in macular and lichen amyloidosis suggests that the epidermis plays a major role in its pathogenesis. Amyloid deposits in macular amyloidosis bind to anti-keratin antibodies and contain sulfhydryl groups, pointing to altered keratin as a source for the deposits. Lichen planus is an immunologically mediated disease that is characterized by violaceous, flat-topped polygonal papules. The exact etiology of lichen planus remains unknown. Recent studies have shown that lichen planus represents a cell mediated immune response to an induced antigenic change in the epidermal cells in a genetically predisposed individual. T cells, both CD4+ and CD8+, accumulate in the dermis, while CD8+T cells infiltrate the epidermis. Histologically macular amyloidosis is characterized by deposition of amyloid in the form of small multifaceted amorphous globules, similar in size to the hyaline bodies found in lichen planus.
Case Report :
A 57- year-old male patient with severely pruritic lesions involving his lower legs and hands for 12 years presented to our out-patient department. It clinically was typical hypertrophic lichen planus. He had been treated with different modalities, including topical and intralesional steroids. He remained disease-free for some time but then the disease recurred. At the time of presentation he had the chief complaint of a new eruption involving his legs, thighs, and arms. Thorough history-taking revealed that the patient had been suffering from diabetes mellitus, asthma and hypertension. There was no family history of similar skin disease.
Cutaneous examination demonstrated hyperkeratotic, violaceous, two to four cm irregular plaques and nodules presented over both the shins and the ankle joints [fig1]. In addition, there were hyperpigmented macules arranged in a rippled pattern over his legs, thighs, and arms [fig2].
On investigation, complete haemogram and thyroid function test were normal. A biopsy specimen of the hyperpigmented macule on thigh revealed normal epidermis and the presence of round, homogeneous, eosinophilic material in the superficial papillary dermis, with a sparse superficial perivascular lymphocytic infiltrate [fig3]. Congo-red stain was consistent with the presence of scanty amount of amyloid [fig4]. A diagnosis of macular amyloidosis was made. A biopsy specimen of the hyperkeratotic nodule on left leg revealed acanthosis, hypergranulosis, papillomatosis, patchy lymphocytic infiltrate along the upper dermis and dermoepidermal junction, along with hydropic degeneration of the basal cell layer at places [fig5]. Adiagnosis of hypertrophic lichen planus was made.The patient was initially given topical steroid and oral antihistamines, but he did not improve. He was put on colchicines 0.5 mg two times daily for two months with regular follow-up, but he did not respond. Finally intralesional steroid was given for hypertrophic lichen planus, and there was some temporary relief from itching, with some of the hypertrophic lesions subsiding considerable.
Chronic irritation to the skin resulting in excessive production of degenerate keratins, and their subsequent conversion into amyloid deposits has been described to be an etiologic factor of primary cutaneous amyloidosis.The concept of focal epidermal damage and filamentous degeneration of keratinocytes, followed by apoptosis and conversion of filamentous masses (colloid bodies) into amyloid material in the papillary dermis, perhaps with a contribution from the dermal-epidermal junction has been proposed, and widely accepted. If the apoptosis theory is true, any damage to the keratinocyte, beyond the ability of the phagocytic cell to remove the abnormal keratins, should be able to cause amyloid deposits. Immunohistochemical staining of amyloid deposits with anti-keratin antibodies has been investigated in several studies. Apaydin et al carried out immunohistochemical investigation on cytokeratins in amyloid deposits in formalin fixed and paraffin-embedded tissue specimens from subjects with macular and lichen amyloidosis to clarify the role of epidermal cells in the pathogenesis of these diseases. Hashimoto et al proposed that degenerate keratins from apoptotic keratinocytes are transformed into amyloid by dermal macrophages and fibroblasts but exact mechanism of the conversion of the alpha tertiary structure of normal tonofilament into the betapleated sheet configuration of amyloid remain unknown. In our case, the patient had chronic lichen planus on both legs before macular amyloidosis developed. Theoretically chronic excessive production of cytoid bodies and disruption of basement membrane can allow degenerated keratins to be processed by macrophages into amyloid filaments later. It is possible that in this case chronic lichen planus produced enough damage at the dermoepidermal junction to induce macular amyloidosis. There have been reports of response of cutaneous amyloidosis to topical DMSO therapy in some but not all. Role of oral colchicines in primary localized cutaneous amyloidosis has been described. Colchicine probably blocks the release oflysosomal enzymes within the degenerated epidermal cells thereby preventing conversion of tonofilaments into amyloid. We have described this patient manifesting both macular amyloidosis and hypertrophic lichen planus, both for the rarity of such case reports, and for the probable aetiological connection between the two. The association, while it may be merely coincidental, raises the interesting possibility that amyloidosis is related to the chronic trauma to the skin, either from chronic pruritus or interface dermatitis.
Fig1. Hypertrophic, violaceous lesions of lichen planus on left leg.
Fig2. Hyperpigmented macules of macular amyloidosis on right thigh.
Fig3. Macular amyloidosis: eosinophilic, hyaline amyloid deposits with pigmentary incontinence in papillary dermis. (H&E, 40X)
Fig4. Macular amyloidosis: homogeneous, globular amyloid deposits in papillary dermis. (Congo-red stain, 40X)
Fig5. Lichen planus: epidermal hyperkeratosis, acanthosis, and hydropic degeneration of basal cell layer with lymphocytic cell infiltration. (H&E, 10X)