Hyperpigmented patches on the back - Clinical Advisor

Hyperpigmented patches on the back

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  • Macular amyloidosis_0414 Derm Clinic 1

A 56-year-old Asian-American man presented with an intensely pruritic rash on his back that had worsened over the past several months. Initially attributing the itch to dry skin, he began to use a daily moisturizer, but the itch did not improve. The man reported constant use of a back-scratcher. No associated fevers, myalgia, joint pains, paresthesias, or prior injuries to his back were noted.

Examination revealed excoriations and poorly demarcated, linear, hyperpigmented patches down the back. A punch biopsy was obtained from one of the darker patches.



HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Excoriations on extensor surfaces and Yellow scalp patches with mild scaling. Then take the post-test here .

Appropriate staining of histologic sections from the punch biopsy confirmed the suspected diagnosis of macular amyloidosis, a type of primary localized cutaneous amyloidosis (PLCA). Amyloidosis is a broad and heterogeneous group of disorders; thus, to best recognize and manage macular...

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Appropriate staining of histologic sections from the punch biopsy confirmed the suspected diagnosis of macular amyloidosis, a type of primary localized cutaneous amyloidosis (PLCA). Amyloidosis is a broad and heterogeneous group of disorders; thus, to best recognize and manage macular amyloidosis, it is essential to understand the disease in its proper context.

It is said that to know amyloidosis is to know medicine. The term amyloid was first used by Virchow in 1854 to describe tissue deposits noted in numerous organs that, when stained with iodine, resembled similarly stained amylum, better known as starch.1

Today, amyloid itself is recognized not as a singular distinct substance but rather as a group of insoluble, extracellular, fibrillar, and proteinaceous materials sharing some common physiochemical properties. These common properties allow for distinctive and characteristic staining patterns with Congo red and crystal violet dyes for amyloid from all sources.

Approximately 18 distinct forms of amyloid and amyloid precursors have been identified, each derived through unique and multifaceted processes (e.g., protein misfolding). When viewed under electron microscopy, amyloid will appear as a meshwork of rigid and nonbranching linear fibers.2

The clinical variability of amyloidosis reflects the different pathogenic processes that result in amyloid production. Amyloidosis is classified broadly into three categories: primary systemic amyloidosis (PSA), secondary systemic amyloidosis (SSA), and organ localized amyloidosis, including PLCA. 


Although amyloid production in PSA may be idiopathic, it is often associated with either a plasma cell dyscrasia or myeloma, with the amyloid fibrils being composed of such processed precursor proteins as immunoglobulin light chains. The precursor proteins are soluble, extensively distributed by the circulatory system, and deposited in multiple organ systems, including mucous membranes, skin, vasculature, neuronal pathways, kidneys, and heart.

Cutaneous findings in PSA may be subclinical, but when visible, skin signs are highly variable, ranging from smooth, waxy skin-colored papules a few millimeters in diameter, to purpuric papules, to nodules and plaques; macroglossia may be present as well.

While diffuse cutaneous deposition is possible, involvement of the palms, face, neck, and anogenital regions is most common. Vascular amyloid deposition causes vascular fragility, making vessels prone to rupture after such minor trauma as a pinch or simple rubbing (so-called “pinch purpura”).2

SSA is a reactive complication of a host of chronic inflammatory conditions, including rheumatoid arthritis, tuberculosis, leprosy, osteomyelitis, and systemic lupus erythematosus. Distinctively, cutaneous findings in SSA are exceedingly rare.2

The three distinctive subtypes of PLCA are macular amyloidosis (MA), lichen amyloidosis (LA), and nodular amyloidosis. Of these, nodular amyloidosis is the rarest, developing in association with localized plasma cell aggregates. Amyloid in MA and LA is exclusively and uniquely keratinocyte-derived, and these two conditions may actually represent a clinical spectrum of the same disease process.2

LA typically develops as confluent, discrete, firm, flesh- colored or hyperpigmented papules, most commonly on the extensor surfaces; the lesions of MA are characteristically found on the upper back presenting as poorly demarcated brown or gray macules or patches (diffuse involvement including the chest and face may occur).3

Although the pathogenesis of MA and LA remains speculative, a widely accepted theory suggests that apoptotic keratinocytes release cellular contents that are uniquely metabolized, producing amyloid K from cytokeratin. Other suspected etiologic cofactors include environmental influences, genetic predisposition, and repetitive or prolonged friction.

Friction (e.g., itching, scratching) is believed to be a critical pathogenic factor in both MA and LA, evoking a self-perpetuating cycle of mechanically induced apoptosis of keratinocytes with subsequent release of cytokeratin, which is intensely pruritic and induces further itching and scratching. The diseases often follow a chronic course, most commonly associated with intractable pruritus (some patients may be asymptomatic). Unlike systemic amyloidosis, cutaneous vascular involvement does not occur in MA and LA.3,4

MA is more common in young adults, with a female predominance of 2:1 to 3:1. The condition predominantly occurs in individuals of South American, Southeast Asian, or Chinese ancestry and is rare in whites; however, an increased incidence has been observed among people living near the equator.5,6

Since the cutaneous lesions are notoriously variable, the clinical differential of MA is broad. MA is commonly misidentified as notalgia paresthetica, post-inflammatory hyperpigmentation, poikiloderma, atopic eczema, lichen simplex chronicus, and fixed drug reactions.3

The diagnosis of MA can be made based on the patient’s history and physical findings; however, confirmation of the diagnosis requires a punch biopsy with appropriate staining or electron microscopy, if available. Amyloid deposits may be small dermal aggregates that are easily overlooked with routine hematoxylin and eosin staining.

Tissue staining with either Congo red or crystal violet dyes will allow the amyloid deposition to become visible; with Congo red staining the sections show a typical apple-green birefringence under polarized light. If electron microscopy is performed, then linear, nonbranching, aggregated fibrils that are 7 nm to 10 nm thick and of indefinite length can be seen arranged in a loose meshwork, typical for amyloid.2,7

Given the relative rarity of the disease, large-scale studies regarding management of MA are scarce. Without a known pathogenic mechanism to manipulate or correct, current therapies focus on symptomatic relief. Patient education on such environmental and behavioral factors as avoiding scratching and excess/chronic friction are essential to break the pathogenic cycle. Use of antihistamines can provide some relief.

Milder cases may respond to potent topical corticosteroids. Other modalities used with varying degrees of success include such mild topical keratolytic agents as salicylic acid, topical or oral dimethyl sulfoxide (DMSO), phototherapy, and oral retinoids. In certain cases of limited disease, surgical excision may be an option.4,8 Health-care providers must balance treatment benefits with potential side effects on a case-by-case basis.


The man described in this case was educated about MA and the paradoxical role that scratching plays in worsening the severity of his pruritus. He was prescribed antihistamines and started on a trial of a high-potency topical corticosteroid. 


Geoffrey A. Bader is a third-year student at Medical College of Virginia Hospitals, Virginia Commonwealth University, in Richmond, where Julia R. Nunley, MD, is a professor of dermatology.



HOW TO TAKE THE POST-TEST: This Clinical Advisor CME activity consists of 3 articles. To obtain credit, you must also read Excoriations on extensor surfaces and Yellow scalp patches with mild scaling. Then take the post-test here .

References


  1. Wong CK. History and modern concepts (cutaneous amyloidosis). Clin Dermatol. 1990;8:1-6.

  2. Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol. 1988;18:1-16.

  3. Wang WJ. Clinical features of cutaneous amyloidosis. Clin Dermatol. 1990;8:13-19.

  4. Schreml S, Szeimies RM, Vogt T, et al. Cutaneous amyloidoses and systemic amyloidoses with cutaneous involvement. Eur J Dermatol. 2010;20:152-160.

  5. Ollague W, Ollague J, Ferretti H. Epidemiology of primary cutaneous amyloidoses in South America. Clin Dermatol. 1990;8:25-29.

  6. Tan T. Epidemiology of primary cutaneous amyloidoses in southeast Asia. Clin Dermatol. 1990;8:20-24.

  7. Li WM. Histopathology of primary cutaneous amyloidosis and systemic amyloidosis. Clin Dermatol. 1990;8:30-35.

  8. Wong CK. Amyloid treatment. Clin Dermatol. 1990;8:108-111.

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