[Monoclonal immunoglobulin (M-Ig) and skin diseases from the group of mucinoses--scleredema adultorum Buschke and scleromyxedema. Description of four cases and an overview of therapies]. / Monoklonální imunoglobulin a kozní nemoci ze skupiny mucinóz--scleredema adultorum Buschke a scleromyxedema: popis 4 prípadu a prehled lécebných mozností.

INTRODUCTION: The mucinoses of the type of scleredema and scleromyxedema are diseases marked by excessive production of mucin deposits in the skin and subcutaneous tissue, which causes skin hardening. The skin and subcutaneous deposits hamper the movement of limbs, the thorax as well as mouth. The same mechanism also damages other organs (the heart, lungs, oesophagus). It is probably caused by the stimulation of mucin production in fibroblasts by immunoglobulins, frequently monoclonal immunoglobulin. Therefore these diseases are typically associated with monoclonal gammopathy. CASE REPORTS: We describe a cohort of 4 patients, skin manifestations were twice identified as scleredema and twice as scleromyxedema. All the four patients had type IgG monoclonal immunoglobulin and had clonal plasma cells in the bone marrow proven by histologic examination and flow cytometry. Therefore we commenced chemotherapy in all of them. In one case this chemotherapy was ended by a high-dose chemotherapy with transplanting of autologous red blood cells. This therapy attained the complete disappearance of monoclonal immunoglobulin as well as cutaneous and extracutaneous manifestations of scleredema (obstipation). In one case chemotherapy led to partial hematologic remission and partial improvement of skin manifestations. The other two patients did not respond to standard chemotherapy. The condition of one of them resulted in dermato-neuro syndrome (confusion, somnolence passing into coma and grand mal seizure) and improved following an intensive treatment including also intravenous application of immunoglobulins in a dose of 2 g/per 1 kg weight. This patient has now been under long-term treatment with these immunoglobulins, during which the skin symptoms have significantly diminished, but the concentration of monoclonal immunoglobulin has not changed. The fourth patient not responding to standard chemotherapy was treated with intravenous immunoglobulins also in a dose of 2 g/per 1 kg of weight 1× in a month. After 4 applications the thickening of skin and subcutaneous tissue moderately diminished, so the range of possible movement of the upper limbs and neck became larger and the itchy skin morphs which accompanied the disease disappeared completely. CONCLUSION: It is possible to use chemotherapy and high-dose chemotherapy in the treatment of mucinosis associated with monoclonal gammopathy, as in the treatment of multiple myeloma. If such treatment is not possible or it has not attained disappearance of monoclonal immunoglobulin, improvement can be achieved through repeated application of intravenous immunoglobulins. The treatment with intravenous immunoglobulins in an immunomodulation dose of 2 g/per 1 kg of weight effects the moderation of skin manifestations, but it does not lead to the decrease in monoclonal immunoglobulin.

Widespread scleredema associated with paraproteinemia and generalized osteoarthritis in an HLA-B39 positive patient.

Scleredema adultorum (SA) is a rare sclerotic disorder characterized by non-pitting induration of the neck with acral progression, sparing hands and feet. We report on a 57-year-old male with severe SA associated 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. Severe 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, increased 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 treatment protocol for this rare disease.

Systemic involvement in scleredema of Buschke associated with IgG-kappa paraproteinaemia.

Scleredema is a rare primary cutaneous mucinosis. Systemic involvement is uncommon and histological confirmation is often lacking. We report a case of a 60-year-old man with scleredema and evidence of mucin deposition on biopsies from multiple extracutaneous sites. The bone marrow, nerve, hepatic and salivary gland involvement seen on histology in our patient has not, to our knowledge, been previously reported in this condition.

Scleredema revisited. A poststreptococcal complication.

Scleredema is a rare connective disease which must be differentiated from scleroderma in childhood. Scleredema is characterized by thickening of the dermis of the neck, head, and upper trunk. We report a case of scleredema in an 8-year-old boy with coincident streptococcal colonization. The patient report demonstrates many of the common features of scleredema, including an associated streptococcal infection, a relatively benign presentation of illness, and the characteristic mucopolysaccharide intradermal staining on skin biopsy. The literature on scleredema is reviewed, focusing on the disease course, differential diagnosis, and an overview of the proposed three subgroups of scleredema. The association of scleredema to a prior streptococcal infection is explored, and a proposed autoimmune pathophysiology of the disease, as it relates to streptococcal infection, is presented.

Paraproteinemia in patients with scleredema. Clinical findings and serum effects on skin fibroblasts in vitro.

Four patients with paraproteinemia and scleredema were studied. Histologic features included marked thickening and fibrosis of the dermis and subcutis. Variable amounts of mucin deposits were detected in the interfibrillar spaces. Serum from one patient significantly stimulated collagen production in normal skin fibroblast cultures, whereas serum from another patient stimulated collagen production in autologous cell cultures. Moreover, serum from one patient stimulated the [35S]sulfate incorporation into the fibroblasts. Circulating serum factors, possibly related to the paraprotein, may enhance the synthesis of extracellular macromolecules by dermal fibroblasts in these patients, thus providing a mechanism for dermal fibrosis.

Scleredema and monoclonal gammopathy: report of two cases.

Two patients had scleredema with monoclonal gammopathy, one of whom was considered to have smoldering multiple myeloma. In one patient, the scleredema cleared without treatment, while in the other, the scleredema and the monoclonal gammopathy persisted unchanged.

[Buschke's scleredema and monoclonal dysglobulinemia: apropos of 3 cases]. / Scléroedème de Buschke et dysglobulinémie monoclonale: à propos de 3 observations.

A monoclonal gammopathy was observed in 3 adult patients with long-term and widespread scleredema (Buschke's disease). There was no evidence of multiple myeloma in any patient. The monoclonal immunoglobulin was in every case of the IgG-kappa type. Bence Jones proteinuria was noted in 1 case (kappa). Deposition of monoclonal IgG-kappa in the skin was not detected by immunofluorescence microscopy. These findings and previous reports of 5 cases suggest that diffuse scleredema may be frequently associated with paraproteinemia, but the role of monoclonal immunoglobulins in the pathogenesis of the disease remains to be clarified.

Scleredema of Buschke with IgA deficiency.

We describe here a case of Scleredema of Buschke in a female patient aged 63 with IgA deficiency. The disorder appeared after an acute episode of tonsillitis, followed by non-pitting, woody hardness of the skin of the face, neck, shoulders and upper part of the trunk. The disorder resolved after 5 months of penicillin treatment.