Scattered Flesh-Colored Papules in a Linear Array in the Setting of Diffuse Skin Thickening

The Diagnosis: Scleromyxedema

A punch biopsy of the upper back performed at an outside institution revealed increased histiocytes and abundant interstitial mucin confined to the papillary dermis (Figures 1 and 2), consistent with the lichen myxedematosus (LM) papules that may be seen in scleromyxedema. Serum protein electrophoresis revealed the presence of a protein of restricted mobility on the gamma region that occupied 5.3% of the total protein (0.3 g/dL). Urine protein electrophoresis showed free kappa light chain monoclonal protein in the gamma region. Immunofixation electrophoresis revealed the presence of IgG kappa monoclonal protein in the gamma region with 10% monotype kappa cells. The presence of Raynaud phenomenon and positive antinuclear antibody (1:320, speckled) was noted. Laboratory studies for thyroid-stimulating hormone, C-reactive protein, Scl-70 antibody, myositis panel, ribonucleoprotein antibody, Smith antibody, Sjögren syndrome–related antigens A and B antibodies, rheumatoid factor, and RNA polymerase III antibody all were within reference range. Our patient was treated with monthly intravenous immunoglobulin (IVIG), and he noted substantial improvement in skin findings after 3 months of IVIG.

FIGURE 1. A and B, Histopathology showed increased histiocytes and abundant interstitial mucin confined to the papillary dermis (H&E, original magnifications ×100 and ×10).

Localized lichen myxedematosus is a rare idiopathic cutaneous disease that clinically is characterized by waxy indurated papules and histologically is characterized by diffuse mucin deposition and fibroblast proliferation in the upper dermis.¹ Scleromyxedema is a diffuse variant of LM in which the papules and plaques of LM are associated with skin thickening involving almost the entire body and associated systemic disease. The exact mechanism of this disease is unknown, but the most widely accepted hypothesis is that immunoglobulins and cytokines contribute to the synthesis of glycosaminoglycans and thereby the deposition of mucin in the dermis.² Scleromyxedema has a chronic course and generally responds poorly to existing treatments.¹ Partial improvement has been demonstrated in treatment with topical calcineurin inhibitors and topical steroids.²

FIGURE 2. Colloidal iron staining showed increased mucopolysaccharides in the papillary dermis (original magnification ×10).

The differential diagnosis in our patient included scleromyxedema, scleredema, scleroderma, LM, and reticular erythematosus mucinosis. He was diagnosed with scleromyxedema with kappa monoclonal gammopathy. Scleromyxedema is a rare disorder involving the deposition of mucinous material in the papillary dermis that causes the formation of infiltrative skin lesions.³ The etiology is unknown, but the presence of a monoclonal protein is an important characteristic of this disorder. It is important to rule out thyroid disease as a possible etiology before concluding that the disease process is driven by the monoclonal gammopathy; this will help determine appropriate therapies.^4,5 Usually the monoclonal protein is associated with the IgG lambda subtype. Intravenous immunoglobulin often is considered as a first-line treatment of scleromyxedema and usually is administered at a dosage of 2 g/kg divided over 2 to 5 consecutive days per month.³ Previously, our patient had been treated with IVIG for 3 years for chronic inflammatory demyelinating polyneuropathy and had stopped 1 to 2 years before his cutaneous symptoms started. Generally, scleromyxedema patients must stay on IVIG long-term to prevent relapse, typically every 6 to 8 weeks. Second-line treatments for scleromyxedema include systemic corticosteroids and thalidomide.⁶ Scleromyxedema and LM have several clinical and histopathologic features in common. Our patient’s biopsy revealed increased mucin deposition associated with fibroblast proliferation confined to the superficial dermis. These histologic changes can be seen in the setting of either LM or scleromyxedema. Our patient’s diffuse skin thickening and monoclonal gammopathy were more characteristic of scleromyxedema. In contrast, LM is a localized eruption with no internal organ manifestations and no associated systemic disease, such as monoclonal gammopathy and thyroid disease.

Scleredema adultorum of Buschke (also referred to as scleredema) is a rare idiopathic dermatologic condition characterized by thickening and tightening of the skin that leads to firm, nonpitting, woody edema that initially involves the upper back and neck but can spread to the face, scalp, and shoulders; importantly, scleredema spares the hands and feet.⁷ Scleredema has been associated with type 2 diabetes mellitus, streptococcal upper respiratory tract infections, and monoclonal gammopathy.⁸ Although our patient did have a monoclonal gammopathy, he also experienced prominent hand involvement with diffuse skin thickening, which is not typical of scleredema. Additionally, biopsy of scleredema would show increased mucin but would not show the proliferation of fibroblasts that was seen in our patient’s biopsy. Furthermore, scleredema has more profound diffuse superficial and deep mucin deposition compared to scleromyxedema. Scleroderma is an autoimmune cutaneous condition that is divided into 2 categories: localized scleroderma and systemic sclerosis (SSc).⁹ Localized scleroderma (also called morphea) often is characterized by indurated hyperpigmented or hypopigmented lesions. There is an absence of Raynaud phenomenon, telangiectasia, and systemic disease.⁹ Systemic sclerosis is further divided into 2 categories—limited cutaneous and diffuse cutaneous—which are differentiated by the extent of organ system involvement. Limited cutaneous SSc involves calcinosis, Raynaud phenomenon, esophageal dysmotility, skin sclerosis distal to the elbows and knees, and telangiectasia.⁹ Diffuse cutaneous SSc is characterized by Raynaud phenomenon; cutaneous sclerosis proximal to the elbows and knees; and fibrosis of the gastrointestinal, pulmonary, renal, and cardiac systems.9 Scl-70 antibodies are specific for diffuse cutaneous SSc, and centromere antibodies are specific for limited cutaneous SSc. Scleromyxedema shares many of the same clinical symptoms as scleroderma; therefore, histopathologic examination is important for differentiating these disorders. Histologically, scleroderma is characterized by thickened collagen bundles associated with a variable degree of perivascular and interstitial lymphoplasmacytic inflammation. No increased dermal mucin is present.⁹ Our patient did not have the clinical cutaneous features of localized scleroderma and lacked the signs of internal organ involvement that typically are found in SSc. He did have Raynaud phenomenon but did not have matlike telangiectases or Scl-70 or centromere antibodies.

Reticular erythematosus mucinosis (REM) is a rare inflammatory cutaneous disease that is characterized by diffuse reticular erythematous macules or papules that may be asymptomatic or associated with pruritus.¹⁰ Reticular erythematosus mucinosis most frequently affects middle-aged women and appears on the trunk.⁹ Our patient was not part of the demographic group most frequently affected by REM. More importantly, our patient’s lesions were not erythematous or reticular in appearance, making the diagnosis of REM unlikely. Furthermore, REM has no associated cutaneous sclerosis or induration.