The patient is a 38-year-old Hispanic woman who presents with a 1-year history of a very pruritic rash over her interscapular area. On examination, she has a circular area of slightly hyperpigmented macules in the interscapular region. The patient complains of pruritus but no pain in the area of the rash. The patient has no other medical problems and has no systemic symptoms. She has no relevant social or family history and does not take any medications.
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Macular amyloidosis is a chronic pigmentary disorder of the skin; it is found with the highest prevalence in Asia, the Middle East, and South America.1-4 Along with lichen amyloidosis and nodular amyloidosis, it comprises one of three major subtypes of primary localized cutaneous amyloidosis, a condition in which amyloid deposition occurs in otherwise normal skin without associated amyloid deposits in systemic organs.4 Macular amyloidosis most commonly presents between the ages of 21 and 50 years in patients with Fitzpatrick skin phenotype III or IV.2-4 It is predominantly seen in women, with an estimated female-to-male ratio approximating 5:1.1-3
Macular amyloidosis is characterized by a rippled pattern of hyperpigmented brown macules characteristically found in the interscapular area of the back.1-5 It is also commonly found on the extensor surfaces of the extremities, and less commonly on the face, breasts, axilla, and buttocks.1-4 Pruritus is the most common symptom associated with macular amyloidosis, though some cases are asymptomatic.2,4
The exact cause of macular amyloidosis remains unknown, though factors such as sunlight exposure, friction, sex, race, genetic factors, Epstein-Barr virus infection, and autoimmune reactions have been proposed.2,4 Classically, frictional rubbing and sunlight exposure are considered the major etiologic drivers of the disease process,1,4 though both of these factors have been challenged by recent studies.2,3 Macular amyloidosis is associated with autoimmune disorders such as systemic lupus erythematosus, dermatomyositis, primary biliary cirrhosis, and atopic dermatitis.1,3,4
The amyloid deposits found in macular amyloidosis are believed to originate from keratin derived from damaged basal keratinocytes; staining of these deposits with monoclonal antibodies such as EKH4 or EAB-903 against the keratin of basal keratinocytes has demonstrated positive reactions.1,4,5 Apolipoprotein E4, as well as type IV collagen and laminin, are also associated with the formation of the amyloid deposits specific to macular amyloidosis.4
The pathogenesis of macular amyloidosis is currently attributed to two major theories — the fibrillary body theory and the secretory theory.2,4 The fibrillary body theory proposes that damaged basal keratinocytes pass into the papillary dermis after undergoing filamentous degeneration, where they are subsequently modified into amyloid material by histiocytes and dermal fibroblasts.2,4 The secretory theory proposes that damaged basal keratinocytes directly secrete amyloid precursor proteins at the epidermo-dermal interface, which then pass through the damaged lamina densa into the papillary dermis.2,4
Macular amyloidosis is typically diagnosed clinically by its rippled pattern of hyperpigmented brown macules. Results of skin biopsies sent for routine histologic analysis can commonly appear normal and may fail to demonstrate the amyloid deposits characteristic of the condition.1,2 If present, characteristic macular amyloidosis biopsy specimens show amorphous amyloid deposits within the dermal papillae, located directly below the epidermis.1 When stained with Congo red, the deposits demonstrate characteristic apple green birefringence under polarized light.2,4 Like the amyloid found in systemic amyloidosis, deposits in macular amyloidosis can be identified with electron microscopy as nonbranching fibrils within biopsy specimens.4
The differential diagnosis for macular amyloidosis should include lichen amyloidosis, notalgia paresthetica, prurigo nodularis, and lichen simplex chronicus.4 The differential diagnosis should also include other skin disorders with pigmentary skin changes, including porphyria, Waldenström macroglobulinemia, colloid milium, and lipoid proteinosis.5
Macular amyloidosis is histologically similar to lichen amyloidosis but can be differentiated by clinical presentation. Lichen amyloidosis presents as hyperpigmented lichenified plaques with a rippled appearance, typically presenting on the shins.4,5 When both macular amyloidosis and lichen amyloidosis appear in the same skin region, biphasic amyloidosis is diagnosed.4
Macular amyloidosis can be difficult to treat.1 High-potency topical steroids applied once or twice daily, along with education on the itch-scratch cycle, are the mainstays of treatment. Reducing friction and rubbing of the affected skin area is a high priority, given the evidence identifying friction as a possible etiologic factor.1 Additionally, intralesional corticosteroids, topical tacrolimus 0.1% ointment, 10% dimethyl sulfoxide topical ointment, psoralen plus ultraviolet A light, tar, and calcipotriol have all been used in trials with varying levels of efficacy.1,2 Etretinate and acitretin therapy have been associated with modest success in reducing symptoms, but relapse after treatment cessation is commonly reported.2 Oral retinoids, amitriptyline, thalidomide, and systemic immunosuppressive agents have also failed to provide unequivocal control of symptoms.1 Recent discoveries regarding the role of interleukin-31 in causing pruritus has prompted research into therapies targeting this cytokine pathway in order to control the itching associated with macular amyloidosis.2
The patient in this case was treated with clobetasol ointment (a high-potency topical steroid). The use of clobetasol twice daily, along with education on avoiding scratching and friction, led to the resolution of the rash and her symptoms of pruritus.
Alex Kolkin, BS, is a medical student, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine.
- 1. James WD, Berger TG, Elston DM, Neuhaus IM. Errors in metabolism. In: James WD, Berger TG, Elston DM, Neuhaus IM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia, PA: Elsevier; 2016:509-513.
- 2. Bandhlish A, Aggarwal A, Koranne RV. A clinico-epidemiological study of macular amyloidosis from North India. Indian J Dermatol. 2012;57:269-274.
- 3. Rasi A, Khatami A, Javaheri SM. Macular amyloidosis: an assessment of prevalence, sex, and age. Int J Dermatol. 2004;43:898-899.
- 4. Groves RW, Black MM. Amyloidosis. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:699-708.
- 5. Rapini RP. Deposition and metabolic diseases. In: Rapini RP, ed. Practical Dermatopathology. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2012:122-124.