CASE REPORT

A 48 year old white woman presented for evaluation of a 12 month history of progressive increasing skin thickness and tightening and recurrent falls. The patient was in her usual state of health until one year before admission when she noticed increased skin pigmentation with diffuse skin thickening, initially on the thighs but progressing to her abdomen and arms. She denied any Raynaud's phenomenon. On examination, the vital signs were normal. Examination was significant for skin thickening and induration of the thighs and arms. There was minimal sclerodactyly and no digital ulcers, scars or synovitis. No nailfold capillary abnormality was noticed. The oral aperture was mildly decreased with no evidence of telangiectasias. There were bilateral flexion contractures of the knees and the elbows. Results of chest, heart, and abdominal examinations were within normal limits. Neurological examination was significant for proximal muscle weakness, 4/5 in the arms and 3+/5 in the legs. Laboratory data showed normocytic normochromic anaemia. Renal panel and urine analysis results were normal. The patient had a serum albumin of 28 g/l with serum calcium of 2.70 mmol/l. Her creatine kinase was 28 U/l and erythrocyte sedimentation rate (Westergren) >100 mm/ 1st h. She had a negative antinuclear antibody test and negative antibodies to smith, ribonucleoprotein, and Scl-70. A lumbar sacral spine x ray examination for back pain showed diffuse osteoporosis with multiple wedge fractures. Investigation for secondary osteoporosis included serum and urine electrophoresis, which showed an IgGλ monoclonal protein on immunofixation. Serum IgG was 36.00 g/l (normal 6.87–16.30) with other immunoglobulins being low normal. A bone marrow biopsy and aspiration was performed which disclosed 25% plasma cells with immunohistochemistry showing increased numbers of λ light chain positive plasma cells and normal chromosomal analysis. This was consistent with IgGλ multiple myeloma.

Full thickness skin, fascia, and muscle biopsy specimens were obtained. The skin biopsy showed evidence of sclerodermatous changes, in which minor epidermal atrophy was associated with modest diffuse hyalinised collagenosis of the dermis. The superficial dermis showed microvascular endothelial swelling, punctate haemosiderosis, and a minimal lymphocytic infiltrate, which contained numerous eosinophils. Mucicarmine and Alcian blue stains were negative. Sections demonstrating fascia and muscle showed a homogeneous collagenosis throughout the fascia, which contained small focal residual islands of perivascular lymphocytosis (fig 1). Congo red reactions were negative for amyloid. Histologically, this was most consistent with eosinophilic fasciitis. The patient was treated with high dose dexamethasone and pamidronate for her MM with mild improvement of her skin induration on two month follow up. The patient, unfortunately, died suddenly at a rehabilitation centre after three months of treatment.

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Figure 1

A thickened, hyalinised amorphous tissue containing small chronic inflammatory foci replaces the fascia. The fascial-epimysial interface is replaced by dense collagen inducing compressional atrophy of adjacent muscle bundles (arrow) (×80).

DISCUSSION

Painful swelling and induration of the skin and underlying soft tissues of the arms and legs clinically characterise EF, first described by Shulman in 1974.¹ Haematological associations are well described with EF, and have evoked most interest and concern. EF has been reported with anaemia and thrombocytopenia, pancytopenia, haemolytic anaemia, lymphadenopathy, and pernicious anaemia.^2–5 Haematological malignancies that have been associated with EF include Hodgkin's disease, lymphoproliferative disorder, angioimmunoblastic lymphadenopathy, peripheral T cell lymphoma and, possibly, acute myeloid leukaemia, acute myelomonocytic leukaemia, and myeloproliferative disorder; each of the last three conditions have been seen in one case of EF.^4–6 Whereas hypergammaglobulinaemia is a well described feature of EF, monoclonal gammopathy has only been reported twice.^7,8

We present the first case report of IgGλ MM associated with EF. The presence of monoclonal gammopathy can also be seen with scleroderma (SSc) like skin diseases including scleromyxoedema and scleredema,^9,10 but the pathogenesis of these diseases is still largely unknown. Sera from patients with scleredema and MM have been shown to stimulate collagen production, both in the normal fibroblasts¹¹ and in the autologous cell cultures,¹¹ suggesting that serum factors produced by the myeloma cells might have a role in the development of dermal thickening. Also, treatment of MM improves the skin disease.¹¹ However, in our patient, the skin was not studded with waxy papules, as seen with scleromyxoedema and the skin biopsy was negative for mucopolysaccharide deposition (negative Alcian blue stain). MM has also been seen in two patients with SSc,³ and a review of the natural history of monoclonal gammopathy in 241 patients showed that 6% had SSc and other autoimmune diseases, but no EF.¹² Furthermore, the two conditions have some additional features in common. Certain cytokine abnormalities are seen in both illnesses. Interleukin 6¹³ and transforming growth factor β are thought to have an important role in both conditions. These findings suggest that certain serum factors, both known and yet to be elucidated, might have contributed to the association of EF with MM.

Our case demonstrates the diverse and serious haematological manifestations that can occur with EF. Rheumatologists should have a high degree of awareness of MM in a patient with EF who presents with monoclonal gammopathy, as the diagnosis has significant therapeutic implications.