Case Report Dermatology 2006;212:366–369 DOI: 10.1159/000092288
Received: July 7, 2005 Accepted: October 2, 2005
Generalized Mucinosis in a Patient with Erythroderma Taku Fujimura Ryuhei Okuyama Satoshi Nakagawa Tadashi Terui Setsuya Aiba Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan
Key Words Erythroderma ! Atypical papular mucinosis
Abstract We describe an 81-year-old Japanese patient with erythroderma overlapping with widespread and symmetrical deposits of mucin in the upper dermis. Clinically, the mucinous lesions on the nape and upper trunk were localized papular mucinosis. Histologically, there was a perivascular infiltrate of lymphohistiocytic cells mingled with plasma cells in the upper dermis but no sclerosis. Immunohistochemical staining revealed that more than 90% of these infiltrating plasma cells produced immunoglobulin !-chain. Both the erythroderma and generalized mucinosis responded to topical steroid and PUVA therapy. To the best of our knowledge, this is the first case of erythroderma accompanied by generalized mucinosis. Copyright © 2006 S. Karger AG, Basel
Introduction
Erythroderma is a cutaneous reaction pattern that can occur in a wide variety of benign and malignant diseases (reviewed by Rothe et al. [1], Sehgal et al. [2] and Bettoli et al. [3]). Dermatitis, including atopic der-
matitis, contact dermatitis, seborrheic dermatitis and chronic actinic dermatitis, psoriasis, drug reactions and cutaneous T cell lymphoma represent the most common underlying causes of erythroderma. Unusual causes include ichthyoses, bullous dermatoses, pityriasis rubra pilaris, Ofuji’s papuloerythroderma and connective tissue diseases. Cutaneous mucinosis can be classified as primary, in which mucin deposition is the main histological feature resulting in clinically distinctive lesions, and secondary, in which mucin simply represents an additional finding [4, 5]. Primary cutaneous mucinosis is further subclassified into lichen myxedematosus, reticular erythematous mucinosis, scleredema, dysthyroidotic mucinosis, cutaneous lupus mucinosis, cutaneous focal mucinosis, digital mucous cyst, follicular mucinosis and other miscellaneous mucinoses [6]. On the other hand, various inflammatory or neoplastic cutaneous disorders are associated with the histological deposition of mucin. In this paper, we describe a patient with erythroderma associated with widespread and symmetrical deposits of mucin. Interestingly, the mucinous lesions on the nape and upper trunk demonstrated clinical pictures similar to localized papular mucinosis. To our knowledge, there is no English report of erythroderma associated with generalized mucinosis.
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Case Report
An 81-year-old Japanese man visited us with a 10-month history of pruritic eruptions on his neck, trunk and extremities. He had been treated with topical steroids and antihistamine for 9 months without any improvement. Physical examination showed erythroderma overlapping with groups of firm, closely spaced, waxy red papules, 3–4 mm in diameter in the nuchal region (fig. 1) and well-demarcated infiltrated erythematous plaques 7 ! 5 cm and 5 ! 4 cm surrounded by normal skin on his chest and back (fig. 2). A full blood count and biochemical profile revealed eosinophilia (22%), increased IgA level (573 mg/dl), a significantly high level of IgE (40,000 IU/ ml) and serum IL-2 receptor (2,558 U/ml), although the IgE radioallergosorbent test (RAST) scores for house dust, tick, cedar, peanut, egg albumin, wheat, soy bean, rice, milk and Pityrosporum were all level 2. There were no hyperproteinemia, paraproteinemia or atypical plasma cells in the bone marrow. The patient was found to be euthyroid by a measurement of the basal TSH and free T4 levels as well as by a TRHprovocative test. We screened for a possible internal malignancy but found none, although an abdominal aortic aneurysm was detected by CT scan. He had been treated with oral intake of imidapril hydrochloride and nifedipine for hypertension 5 years be-
Taku Fujimura Department of Dermatology, Tohoku University Graduate School of Medicine Seiryo-machi 1-1, Aoba-ku Sendai, 980-8574 (Japan) Tel. +81 22 717 7271, Fax +81 22 717 7275, E-Mail
[email protected]
fore, and we changed these drugs to benidipine hydrochloride and candesartan cilexetil soon after he had visited our clinics without improvement of his eruptions. The histopathological pictures of the lesions on the nuchal region and those on the back were similar and showed band-like deposits of alcian blue-positive mucin and a perivascular infiltrate of lymphohistiocytic cells mingled with plasma cells in the upper dermis but no sclerosis (fig. 3). Immunohistochemical staining revealed that more than 90% of these infiltrating plasma cells produced immunoglobulin !-chain (fig. 4). We treated him with PUVA 5 times a week for 6 weeks and topical application of 0.1% diflucortolone valerate ointment twice a day. Most lesions had cleared by 5 weeks after the start of the treatment and remained under control with the same ointment. Discussion
The present case was unique in terms of its clinical findings, i.e. the association of erythroderma with generalized mucinosis. It is well known that erythroderma is associated with a variety of cutaneous or systemic diseases, such as eczematous dermatitis, psoriasis, drug eruptions, cutaneous T cell lymphoma and internal malignancies. Therefore, we examined the cause of erythroderma in this patient, especially to rule out a possible association with systemic diseases. We could not find thyroid dysfunction or any associated internal malignancies. The histopathological findings of 3 biopsy specimens excluded the presence of either psoriasis or cutaneous T cell lymphoma. We changed the patient’s intake of oral drugs for hypertension soon after he had visited our clinic, but there was no improvement. Therefore, we considered his erythroderma to be idiopathic erythroderma which is commonly observed in elderly men. The spongiosis and perivascular infiltrate of mononuclear cells supported the diagnosis. However, the histopathological findings of 3 biopsies from different sites were inconsistent with idiopathic erythroderma because of the band-like deposits of mucin in the upper dermis. Although mucin can deposit as follicular mucinosis in cutaneous T cell lymphoma, to our knowledge, there has been no report of erythroderma showing generalized mucinosis. Conversely, this case can be interpreted as a peculiar type of mucinosis developing erythroderma. Again, there has been no English report of such a case.
Generalized Mucinosis in a Patient with Erythroderma
Fig. 1. Erythroderma slightly sparing abdominal positional folds.
Fig. 2. Erythroderma overlapping with groups of firm, closely spaced, waxy red papules, 3–4 mm in diameter, in the nuchal region. A A well-demarcated infiltrated erythematous plaque of 5 ! 4 cm surrounded by normal skin on his back. B Close-up view of the upper right part of the back.
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3 Fig. 3. Histological sections of lesions from the nape. A Hematox-
ylin-eosin stain revealed band-like mucin deposits in the upper dermis and a superficial perivascular infiltrate composed of mononuclear cells and plasma cells. Original magnification !50. B Alcian blue stain revealed the presence of abundant mucin. Original magnification !50. Fig. 4. The immunohistochemical staining of immunoglobulin light chains revealed the preferential expression of !-chain by infiltrating plasma cells. A Immunoglobulin !-chain. Original magnification !200. B Immunoglobulin "-chain. Original magnification !200.
Clinically, this patient presented two distinct types of cutaneous lesions, although his skin condition could be grossly classified into erythroderma, namely the lesions of the nuchal region were composed of closely spaced groups with firm, waxy papules, while there was a well-demarcated erythematous plaque surrounded by normal skin in the lesions of his upper chest and back. The lesions of the arm showed diffuse, infiltrated erythema. Histologically, all lesions demonstrated band-like deposits of mucin in the upper dermis with the densest deposits in those of the nuchal lesion and the fewest deposits in those of the arm. There was a perivasclar infiltrate of mononuclear cells and plasma cells in the upper dermis. Considering these clinical and histopathological findings, we diagnosed the grouped papules in the nuchal region and the erythematous
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plaques on the upper chest and back as lichen myxedematosus. Lichen myxedematosus is a chronic disorder characterized by lichenoid papules, nodules and/or plaques due to dermal mucin deposits and a variable degree of fibrosis in the absence of thyroid diseases [4]. Lichen myxedematosus includes two clinicopathological subsets: a generalized papular and sclerodermoid form (also called scleromyxedema) and a localized papular form. In addition to the difference in cutaneous lesions, scleromyxedema differs from the localized papular form in the presence of monoclonal gammopathy. Recently, a third group composed of atypical or intermediate forms, not meeting the criteria of either scleromyxedema or the localized form, has been reported. Since our case was not accompanied by monoclonal gammopathy, the nuchal le-
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sions can be classified into a localized, papular form of lichen myxedematosus. Recently, Clark et al. [7] have described a case of atypical papular mucinosis with a definite plasma cell dyscrasia which preferentially expressed immunoglobulin !-chain in the in situ hybridization. Interestingly, this case was not accompanied by demonstrable serum monoclonal paraprotein [7]. Clark et al. [7] suggested that the absence of serum paraprotein or marrow plasmacytosis did not exclude the existence of a plasma cell neoplasm in patients with papular mucinosis if the infiltrating plasma cells preferentially express !-chain, because the normal human ":! ratio is approximately 1:2. Similarly, the infiltrating plasma cells in our case also preferentially expressed !-chain, suggesting that these plasma cells were neoplastic.
Fujimura/Okuyama/Nakagawa/Terui/ Aiba
Unexpectedly, this patient had an extremely high level of serum IgE without a significantly high RAST score to any environmental or food allergens. We examined the IgE expression on the infiltrating plasma cells in the present case, and none were stained with anti-IgE antibody (data not
References
Generalized Mucinosis in a Patient with Erythroderma
shown). Similarly, we have not yet determined the cause of the high serum IL-2 receptor. Since there is no established therapeutic modality for generalized mucinosis, we treated this case with PUVA and topical steroid targeting erythroderma. Interestingly,
this treatment improved his erythroderma as well as the mucinosis in a short time, although the serum level of IgE remained extremely high. Considering the clinical response to the treatment targeted at erythroderma, we think that generalized mucinosis is secondary to erythroderma.
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