Extremely pruritic ­hyperkeratotic papules - Clinical Advisor

Extremely pruritic ­hyperkeratotic papules

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  • Lichen amyloidosis_0712 Derm Clinic

A black man, aged 55 years, presented with a 10-year history of a very itchy rash on both lower legs. He admitted to scratching and reported that several courses of prednisone had provided no relief. Seasonal allergies and asthma as an infant were his only medical issues.

No cardiac, GI or other skin problems were detected. The man works as a trainer at an athletic club. Physical examination revealed 3- to 4-mm hyperkeratotic and hyperpigmented papules coalescing into plaques on the anterior portions of both lower legs. 



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The clinical and histologic findings were consistent with the diagnosis of lichen amyloidosis, a type of primary localized cutaneous amyloidosis. A punch biopsy of one of the papules revealed epidermal hyperkeratosis and acanthosis of the epidermis with eosinophilic deposits in...

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The clinical and histologic findings were consistent with the diagnosis of lichen amyloidosis, a type of primary localized cutaneous amyloidosis. A punch biopsy of one of the papules revealed epidermal hyperkeratosis and acanthosis of the epidermis with eosinophilic deposits in the papillary dermis. Congo red staining of the dermal deposits demonstrated apple-green birefringence under polarized light, which is diagnostic of amyloidosis. Laboratory testing for an abnormal immunoglobin spike was negative.

Amyloidosis is not a single disease but rather a group of diseases, each of which is characterized by the deposition of extracellular amyloid, a fibrillar proteinaceous material derived from various sources. Amyloidosis may occur as a systemic disease or be limited to a specific organ.

Systemic amyloidosis may be primary or secondary. Primary amyloidosis occurs in the setting of a plasma-cell dyscrasia, such as myeloma, and the resultant amyloid is from the abnormally produced light chains classified as “AL.” Secondary systemic amyloidosis is seen in association with a variety of chronic inflammatory conditions (e.g., rheumatoid arthritis) or inherited conditions (e.g., familial Mediterranean fever); in these situations the amyloid produced is termed “AA.”

Primary localized cutaneous amyloidosis is skin-limited and can be classified into the subsets lichen amyloidosis, macular amyloidosis, nodular amyloidosis, and familial amyloidosis. Of these subsets, lichen amyloidosis is the most common.

First described in 1928 by Gutmann, lichen amyloidosis is seen most often in individuals of Chinese, Southeast Asian or South American descent.1 It is more common in men and typically presents in the fifth or sixth decade of life. The initial presentation appears to be an intense itch that causes the patient to scratch relentlessly. This constant scratching causes significant mechanical trauma to the keratinocytes of the epidermis.

Subsequently, filamentous degradation and apoptosis of the basal keratinocytes eventually forms colloid bodies. These colloid bodies are ultimately broken down into amyloid K, or “AK” (for keratinocyte), which remains within the papillary dermis.2 Over time, these deposits accumulate, causing the characteristic small, numerous, red-brown, hyperkeratotic papules that may coalesce into plaques. Whereas the most common location for lichen amyloidosis is the pretibial area, other areas affected include the calves, ankles, thighs, dorsal feet, forearms, concha of the ears, anosacral area and interscapular areas.3,4

The pathogenesis of lichen amyloidosis is not fully understood. Most cases are sporadic, but up to 10% of patients report a family history, suggesting a genetic predisposition.4 Lichen amyloidosis has been reported in association with a variety of cutaneous disorders, many of which are pruritic dermatoses, including atopic dermatitis, lichen planus and notalgia paresthetica. However, recent data have cast some doubt on the itch-scratch pathogenesis of the condition.

A skin biopsy will establish the diagnosis. Routine hematoxylin and eosin staining demonstrates hyperkeratosis and acanthosis of the epidermis with eosinophilic deposits in the papillary dermis; increased numbers of melanophages and fibroblasts may be seen in the papillary dermis as well.3

Congo red staining identifies the deposits as amyloid via the characteristic apple-green birefringence under polarized light. Additional stains can be used for confirmation; methyl violet or crystal violet will stain amyloid metachromatically, and thioflavin T will confer amyloid with a yellow-green birefringence under fluorescence microscope.4

The differential diagnosis of the hyperpigmented pruritic papules and plaques seen in lichen amyloidosis is broad and includes macular amyloidosis, nodular amyloidosis, systemic amyloidosis, lichen simplex chronicus, lichen planus and prurigo nodularis.

Although macular and lichen amyloidosis are somewhat similar in presentation, they may be differentiated histologically. Whereas both conditions demonstrate amyloid deposition with special staining, lichen amyloidosis manifests hyperkeratosis and acanthosis, which is minimal or absent in macular amyloidosis.4 Interestingly, the two conditions occasionally coexist, a diagnosis known as biphasic amyloid­osis. Nodular amyloidosis is distinguished by the presence of plasma cells. Although histologically similar, the amyloid of nodular amyloidosis is chemically distinct from either macular or lichen amyloidosis.

By definition, none of the primary localized cutaneous amyloidoses have systemic involvement. However, various organ systems are affected in systemic amyloidosis, most commonly the heart, GI tract and skin. A thorough review of symptoms should be part of the initial evaluation of all patients suspected of amyloidosis. Pruritus, extremely common in lichen and macular amyloidosis, is generally absent in systemic amyloidosis.5 The most common skin finding of systemic amyloidosis is purpura caused by vessel involvement and interference with clotting factor X.

Relief of pruritus is the main treatment goal. Some of the more effective medications include the sedating antihistamines, topical ultra-potent corticosteroids, topical immune modulators and topical dimethylsulfoxide.4 Phototherapy and dermabrasion have also been used.6 Broadband UVB, narrowband UVB and photochemotherapy with psoralen plus UVA reportedly have the same success rate as that of topical steroids.6 Unfortunately, this disease remains very difficult to treat, and complete remission is rare.4

This patient was treated with the topical ultra-potent steroid clobetasol applied b.i.d. Minimal improvement was noted after four weeks. Sedating antihistamines interfered with his work, and nonsedating antihistamines were minimally effective. Narrow-band UVB phototherapy appeared to be the most effective, but returning to the clinic two to three times a week for treatment has been costly and inconvenient.

Adam J. Carter is a fourth-year medical student at Virginia Commonwealth University School of Medicine in Richmond. Julia R. Nunley, MD, is professor of dermatology at Medical College of Virgina Hospitals, also in Richmond.

References

1. Gutmann C. Amyloidosis of the skin. Ned Tijdschr Geneeskd. 1928;2: 4480-4483.

2. Huilgol SC, Ramnarain N, Carrington P et al. Cytokeratins in primary cutaneous amyloidosis. Australas J Dermatol. 1998;39:81-85.

3. Oiso N, Yudate T, Kawara S, Kawada A. Successful treatment of lichen amyloidosus associated with atopic dermatitis using a combination of narrowband ultraviolet B phototherapy, topical corticosteroids and an antihistamine. Clin Exp Dermatol. 2009;34:e833-e836.

4. Tanaka A, Arita K, Lai-Cheong JE, et al. New insight into mechanisms of pruritus from molecular studies on familial primary localized cutaneous amyloidosis. Br J Dermatol. 2009;161:1217-1224.

5. Weyers W, Weyers I, Bonczkowitz M, et al. Lichen amyloidosus: a consequence of scratching. J Am Acad Dermatol. 1997;37:923-928.

6. Jin AG, Por A, Wee LK, et al. Comparative study of phototherapy (UVB) vs. photochemotherapy (PUVA) vs. topical steroids in the treatment of primary cutaneous lichen amyloidosis. Photodermatol Photoimmunol Photomed. 2001;17:42-43.

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