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Papulonodular mucinosis in systemic lupus erythematosus

  • Author(s): Ortiz, Victoria G, MD
  • Krishnan, Ravi S, MD
  • Chen, Ling L, MD
  • Hsu, Sylvia, MD
  • et al.
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Papulonodular mucinosis in systemic lupus erythematosus
Victoria G Ortiz MDa, Ravi S Krishnan MDa, Ling L Chen MDb, and Sylvia Hsu MDa
Dermatology Online Journal 10 (2): 16

Department of Dermatology, Baylor College of Medicine, Houston, Texasa University of Texas Southwestern Medical Center, Dallas, Texasb. shsu@bcm.tmc.edu

Abstract

A 41-year-old man with systemic and serological manifestations of systemic lupus erythematosus presented with a diffuse eruption comprising annular plaques. Histopathology revealed diffuse deposition of mucin throughout the dermis, consistent with papulonodular mucinosis. This uncommon entity of unclear pathogenesis has been described in systemic lupus erythematosus, discoid lupus erythematosus, and subacute cutaneous lupus erythematosus.



Introduction

The cutaneous mucinoses are connective-tissue disorders characterized by the accumulation of mucin in the interstitial spaces of the dermis and within the hair follicle. They may be primary (metabolic) or secondary (catabolic) processes. Papulonodular mucinosis is a distinctive cutaneous manifestation of systemic lupus erythematosus, discoid lupus erythematosus, or subacute cutaneous lupus erythematosus; it is characterized by a diffuse deposition of mucin in the dermis. We describe a patient with systemic lupus erythematosus who subsequently developed papulonodular mucinosis. It is important for clinicians to be aware of and recognize this atypical manifestation; it may be the presenting feature of systemic lupus erythematosus.


Clinical synopsis


Figure 1
Indurated, annular plaques on the arm.

The patient is a 41-year-old man with a past medical history significant for diabetes mellitus. He was referred for evaluation of an eruption over his extremities, face, and trunk. The patient reported that the eruption began approximately 7 months earlier. Since the onset of his skin lesions, the patient admitted that he had had fatigue and joint pains, but he denied any other symptoms, including pruritus, photosensitivity, fevers, Raynaud phenomenon, weight loss, mucous membrane lesions, and neuropsychiatric symptoms.

Physical examination was remarkable only for multiple indurated, annular plaques without scale on the extremities (Fig. 1), trunk, and face. The plaques were skin colored with hyperpigmented centers.


Figure 2 Figure 3
Marked increase in mucin in the dermis. (H&E 400x) (Fig. 2).
Superficial and deep perivascular lymphocyte infiltrate with increased mucin deposition in the dermis. (H&E 100x) (Fig. 3).

A total of five biopsies were taken from lesions on the patient's trunk and extremities. Three of the five biopsies demonstrated a marked increase in mucin throughout the full thickness of the dermis without any other changes consistent with cutaneous lupus (Fig. 2). The fourth biopsy revealed a similar increase in mucin deposition with vacuolar changes at the dermoepidermal junction and a superficial and deep perivascular lymphocytic infiltrate. The fifth biopsy was similar to the fourth but had only scant interface dermatitis (Fig. 3).

Laboratory studies revealed a mild anemia (hemoglobin 12.4 g/dL, hematocrit 36.1 %). White blood cells, platelets, liver function tests, C-reactive protein, creatine kinase, angiotensin-converting enzyme, thyroglobulin antibodies, thyroid peroxidase antibodies, HIV antibodies, cryptococcal antigen, RPR, BUN, and creatinine were all negative or within normal limits. The patient had an ANA titer of 1:320 in a speckled pattern. Anti-Smith and anti-RNP antibodies were also positive. C3 and C4 levels were decreased. However, anti-dsDNA antibodies, anti SCL-70 antibodies, anti-SSA, and anti-SSB were negative. Serum protein electrophoresis did not show hypergammaglobuminemia or paraproteinemia. Urinalysis revealed 2+ protein, and a subsequent renal biopsy revealed lupus nephritis.

The patient was referred to a nephrologist and a rheumatologist and was started on prednisone (60 mg daily) and mycophenolate mofetil (500 mg twice daily).


Discussion

Papulonodular mucinosis, also termed nodular cutaneous lupus mucinosis, was first reported in 1954[1] by Gold, who described an unusual papular eruption seen in systemic lupus erythematosus. It has since been reported in patients with systemic lupus erythematosus [2-17], discoid lupus erythematosus [2, 18], and subacute cutaneous lupus erythematosus [19]. Clinically, papulonodular mucinosis often presents as asymptomatic skin-colored papules and nodules that can be seen within or outside of the typical lesions of lupus erythematosus. It typically involves the trunk and upper extremities; however, the face and other areas of the body may also be affected. Histopathologic examination reveals abundant deposits of mucin located primarily in the papillary and mid-dermis, interspersed among collagen bundles. There may be a slight perivascular lymphocytic infiltrate in the papillary dermis. Although mucin can be demonstrated by histologic examination with staining in the majority of lupus erythematosus patients, it is usually not present in quantities large enough to form clinically detectable papules or nodules. Furthermore, papulonodular mucinosis often lacks other microscopic features of lupus erythematosus, and it can occur in areas clinically free of classic lupus erythematosus. Direct immunofluorescence may show linear or granular deposits of IgG, IgM, and C3 at the basement-membrane zone [2]. Although once perceived as a rare condition, papulonodular mucinosis was found to occur in 1.5 percent of patients with lupus erythematosus in one series [20].

Papulonodular mucinosis can be confused with lichen myxedematosus, a chronic disorder characterized by infiltrative skin lesions in the absence of thyroid disease and, in many cases, the presence of a serum monoclonal paraprotein [21]. The histopathology of lichen myxedematosus is similar to that of papulonodular mucinosis and demonstrates a relatively normal epidermis with increased dermal deposition of mucin and increased collagen bundles in the upper- and mid-dermis. However, lichen myxedematosus is readily distinguished by its clinical presentation: small, densely grouped papules that occur primarily on the face and arms, and an absence of the features of lupus erythematosus. The phenomenon of secondary mucin deposition, which characterizes papulonodular mucinosis in lupus erythematosus, has also been described in other connective tissue diseases, including scleroderma and dermatomyositis [11].

Several factors may contribute to the pathogenesis of this condition. It has been reported that exposure to ultraviolet light can aggravate papulonodular lesions [3]. It has also been postulated that androgens or other sex-related factors may play a role in the pathogenesis of papulonodular mucinosis, because the male-to-female ratio of patients with papulonodular mucinosis is much greater than the male-to-female ratio of those with SLE [2, 18]. In a review of cases, Lowe et al. found a 31 percent incidence of papulonodular mucinosis in male patients [2].

Pandya et al. demonstrated that fibroblasts from affected patients produce more glycosaminoglycans than normal fibroblasts. Their observations suggest that there are serum factors, such as immunoglobulins or cytokines, present in patients with papulonodular mucinosis that upregulate the synthesis of mucin from fibroblasts [4]. Furthermore, they observed that the papulonodular lesions increased concomitantly with serum titers of circulating antibodies, suggesting that these antibodies may drive the increase in the synthesis of glycosaminoglycans. However, other studies have found the temporal relationship of papulonodular mucinosis with lupus erythematosus to be variable; in some cases it has been found to predate lupus erythematosus; in others it is related to lupus erythematosus activity [4]. It remains unclear whether circulating antibodies play a causative role in the aberrant overexpression of glycosaminoglycans by dermal fibroblasts in lesions of papulonodular mucinosis in lupus erythematosus.

Approximately one-half of patients with papulonodular mucinosis have associated kidney disease, and slightly more than half have arthritis. In one series, 80 percent of patients with papulonodular mucinosis had either joint or renal involvement [3]. The high frequency of kidney disease in patients with systemic lupus erythematosus and papulonodular mucinosis suggests that clinicians should have a high index of suspicion for renal involvement. Our patient did not have symptoms of renal disease, and he had normal BUN and creatinine levels, yet a kidney biopsy demonstrated lupus nephritis.

The response of papulonodular mucinosis to treatment has been found to be variable. The minority of cases respond to antimalarials; the rest often require additional treatment with systemic corticosteroids. Rarely, the papulonodular eruption is refractory to both antimalarial therapy and topical or oral corticosteroids [2]. Injection of lesions with hyaluronidase has also been reported to be effective [11, 12].

References

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