Branislava Milenković

Darko Antić

Dušan Škiljević

Ljiljana Medenica

Svetlana Popadić

English

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191ACTA DERMATOVENEROLOGICA CROATICAActa Dermatovenerol Croat 2011;19(3):191-194 CASE REPORTWidespread Scleredema Associated with Paraproteinemia  and Generalized Osteoarthritis in an HLA-B39 Positive PatientSvetlana Popadić1, Dušan Škiljević1, Darko Antić2, Branislava Milenković3, Ljiljana Medenica11Clinic of Dermatology and Venereology, Clinical Center of  Serbia, Department of Der-matology and Venereology, Faculty of Medicine, University of Belgrade; 2Clinic of He-matology, Clinical Center of Serbia; 3Clinic for Lung Diseases and Tuberculosis, Clinical Center of Serbia, Department of Pulmology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.Corresponding author:Profesor Ljiljana Medenica, MD, PhD Clinic of Dermatovenereology Faculty of Medicine, University of Belgrade11000 BelgradeSerbiamedenicaljiljana@yahoo.comReceived: January 7, 2011Accepted: July 15, 2011SummAry Scleredema adultorum (SA) is a rare sclerotic disorder charac-terized by non-pitting induration of the neck with acral progression, spar-ing hands and feet. We report on a 57-year-old male with severe SA associ-ated with paraproteinemia, treated with methotrexate. Such widespread skin thickening followed by severe movement restriction and inability to function on daily basis, as in our patient, has never been described. Se-vere osteoarthritis and finding of HLA-B39 allele in association with SA has not been previously described either. To the best of our knowledge, up to 40 patients with SA associated with paraproteinemia has been reported so far, and currently, there is no established effective treatment protocol. In our patient, low-dose methotrexate resulted in stiffness reduction, in-creased motility of the trunk and extremities, and ability to function on daily basis. We believe that any information about treatment outcome in SA patients should be disseminated in order to establish consensual treat-ment protocol for this rare disease.Key WOrdS: scleredema, paraproteinemia, HLA-B39, osteoarthritisIntrOduCtIOnScleredema adultorum (SA) is a rare sclerotic dis-order characterized by diffuse swelling and non-pit-ting induration of the skin due to thickening of the dermis (1,2). Occurrence of SA has been documented in association with infections (type 1), paraprotein-emia (type 2) and diabetes mellitus (type 3) (1,3). Women are diagnosed with type 1 and type 2 SA ap-proximately twice as frequently as men (1). The SA may be self-limiting, but in patients with progressive disease, therapeutic options are poor. The presence of HLA-B39 allele may be associated with severe os-teoarticular affection (4,5). We report on a patient with SA associated with paraproteinemia, HLA-B39 allele and severe osteoar-thritis. Such marked restriction of the spine, arm and leg movements due to widespread skin stiffness as-sociated with osteoarthritis as in our patient has nev-er been described. After 4-week therapy, low-dose methotrexate induced regression of stiffness and led to increased mobility of the trunk and extremities.CASe rePOrt A 57-year-old male presented with 2-year history of painless, progressive, widespread skin thickening, 192 ACTA DERMATOVENEROLOGICA CROATICAwoody induration of the skin on the neck, shoulders, trunk, arms, and legs (Fig. 1). Skin thickening and stiff-ness appeared gradually during two to three months. His face, hands and feet were spared; Raynaud’s phe-nomenon and telangiectasia were absent. Widespread stiffness led to marked restriction of the spine, arm and leg movement (Fig. 2) and impaired thoracic move-ments with moderate restrictive ventilatory defect. He had personal history of generalized osteoar-thritis and coxarthrosis complicated with lesions of peripheral nerves, alcoholism, osteopenia, compres-sive fractures of L 3-4 and severe obstructive sleep apnea syndrome. During one year, he was observed at Rheumatology Department as possible eosinophil-ic fasciitis (EF) and was treated with low to moderate dose of prednisone. In the absence of relevant labora-tory finding supporting EF diagnosis, normal finding of deep muscle biopsy and failure of corticosteroid therapy, the patient was referred to dermatologist.At presentation, there were no abnormalities in complete blood count, serum and urine biochemi-cal analysis except for decreased serum protein level (54g/L), with slightly reduced beta 1 (5.5%) globulin fraction. Antinuclear antibodies were negative; CH50, circulating immune complexes and immunoglobulin level were normal. HLA typing revealed HLA-A3/23; HLA-B39/44 alleles.Skin biopsy (alcian blue pH 2.5) revealed minimal epidermal changes and a markedly thickened dermis with swollen and separated collagen fibers (Fig. 3). Congo red and toluidine blue staining were negative. The diagnosis of monoclonal gammopathy of un-determined significance (MGUS) was made based on the finding of paraprotein of the IgG lambda type in urine and serum, and absence of malignant cells in bone marrow.Four-week methotrexate (10 mg/week) was re-sulted in significant regression of induration on the Figure 1. Maximal extension of the trunk and extre-mities due to widespread skin thickening and severe osteoarthritis.Figure 2. Maximal adduction of upper and lower limbs.Popadić et al. Acta Dermatovenerol CroatScleredema in HLA-B39 positive patient 2011;19(3):191-194193ACTA DERMATOVENEROLOGICA CROATICAneck, shoulders and upper extremities, with increased motility of the shoulder and arms. After four-month treatment, stiffness of the upper parts of lower ex-tremities was also reduced. dISCuSSIOnScleredema adultorum is a rare sclerotic disease characterized by non-pitting induration of the neck with acral progression, sparing hands and feet. The absence of Raynaud’s phenomenon and visceral in-volvement permits clinical differentiation of this rare disease from systemic sclerosis (2,3). In our patient, the diagnosis of SA was established since clinical and paraclinical findings indicated ab-sence of systemic involvement, deep muscle biopsy demonstrated normal finding, and skin histopathol-ogy indicated mucin deposits in the dermis.Such widespread skin thickening followed by re-striction of trunk and extremity movements as in our patient has never been described. In most patients, SA tends to be localized (6), while type 2 SA tends to assume a progressive course (7). Severe obstructive sleep apnea syndrome is re-ported in 25% of SA patients (6). Paraproteinemia is also found in 25% of SA patients. It has already been documented that MGUS frequently precedes mul-tiple myeloma and that patients with SA tend to have a more aggressive and rapidly progressive multiple myeloma (7). Therefore, patients with SA associated with paraproteinemia should be carefully followed by hematologists.According to the available data, numerous thera-pies for SA have been tried including pituitary extract (1), thyroid hormone (1), colchicine (3), methotrex-ate (8), antibiotics (1), corticosteroids (1,3), electron beam therapy (3,9), physiotherapy (1,3), photophere-sis (1,3), and phototherapy with psoralen (1,3), but none has proved consistently effective (9).To the best of our knowledge, up to 40 patients with scleredema associated with paraproteinemia have been reported. According to literature data, only one patient with type 3 SA treated with low-dose methotrexate partially responded to therapy (8). In our patient, low-dose methotrexate led to reduced skin thickening and better mobility of the shoulder, upper and lower extremities. The finding of HLA-B39 allele has not been reported so far in SA patients and may explain development of severe osteoarticular manifestation in our patient (4).We believe that all information about successful treatment outcome in SA patients may expand the available data pool and provide more management options to physicians. COnCLuSIOnWe present a severe type 2 SA in an HLA-B39 posi-tive male. In our patient, the association of SA and severe osteoarthritis led to reduced motility of the trunk and extremities and inability to function on a daily basis. Treatment with methotrexate resulted in increased motility and improved his quality of life. In order to establish consensual treatment proto-col for this rare disease and to improve patient quality of life, any information about treatment outcome in patients with SA should be disseminated.Acknowledgment This work was partly supported by the Ministry of Science of the Republic of Serbia, grant No. 175038.references1. Beers WH, Ince A, Moore TL. Scleredema adul-torum of Buschke: a case report and review of the literature. Semin Arthritis Rheum 2006;35:355-9.2. Majumder S, Mandal SK, Chowdhury SR, Ban-dyopadhyay D, Bandyopadhyay R, Chakraborty PP. Scleredema of Buschke: a rare post-strep-tococcal complication. J Assoc Physicians India 2007;55:737-8.3. Foti R, Leonardi R, Rondinone R, Di Gangi M, Le-onetti C, Canova M,et al. Scleroderma-like disor-ders. Autoimmun Rev 2008;7:331-9.4. Bravo MJ, Colmenero Jde D, Alonso A, Caballero A. HLA-B*39 allele confers susceptibility to osteo-articular complications in human brucellosis. J Rheumatol 2003;30:1051-3.Figure 3. Alcian blue pH 2.5 staining demonstrating abundant mucin deposits between thickened and se-parated collagen bundles. (magnification, 25X)Popadić et al. Acta Dermatovenerol CroatScleredema in HLA-B39 positive patient 2011;19(3): 191-194194 ACTA DERMATOVENEROLOGICA CROATICA5. Yamaguchi A, Tsuchiya N, Mitsui H, Shiota M, Oga-wa A, Tokunaga K, et al. Association of HLA-B39 with HLA-B27-negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in Japanese patients. Evidence for a role of the peptide-anchoring B pocket. Arthritis Rheum 1995;38:1672-7.6. Ray V, Boisseau-Garsaud AM, Ray P, Pont F, Lin L, Helenon R,et al. Obesity persistent sclerede-ma: study of 49 cases. Ann Dermatol Venereol 2002;129:281-5.7. Dziadzio M, Anastassiades CP, Hawkins PN, Potter M, Gabrielli A, Brough GM, et al. From scleredema to AL amyloidosis: disease progression or coinci-dence? Review of the literature. Clin Rheumatol 2006;25:3-15.8. Seyger MM, van den Hoogen FH, de Mare S, van Haelst U, de Jong EM. A patient with a severe scleroedema diabeticorum, partially respon-ding to low-dose methotrexate. Dermatology 1999;198:177-9.9. Angeli-Besson C, Koeppel MC, Jacquet P, An-drac L, Sayag J. Electron-beam therapy in scle-redema adultorum with associated monoclo-nal hypergammaglobulinaemia. Br J Dermatol 1994;130:394-7.Popadić et al. Acta Dermatovenerol CroatScleredema in HLA-B39 positive patient 2011;19(3): 191-194Use Nivea cream also by cloudy weather; year 1936.(from the collection of Mr. Zlatko Puntijar)

Widespread Scleredema Associated with Paraproteinemia and Generalized Osteoarthritis in an HLA-B39 Positive Patient

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