BALTIMORE — Intravenous immunoglobulin appears to be a safe and effective treatment for scleromyxedema, Dr. Francesco Boin said at a conference on rheumatic diseases sponsored by the Johns Hopkins University.
Scleromyxedema is a rare—though probably underrecognized—disorder that mimics scleroderma. It is characterized by widespread thickened skin and multisystem disease caused by mucinous deposition in the skin and internal organs. It has been described worldwide, with males and females equally affected, and both black and white patients reported in the United States. Mean age of diagnosis is about 55 years, ranging from 30 to 80.
Patients typically present with waxy, bumpy skin, initially in patches but later becoming confluent and generalized and eventually thickened and pendulous. Skin changes behind the ears are almost always present. “The buzzword is the ear … It's a very important spot to check if you're suspicious for this entity,” said Dr. Boin, of the division of rheumatology at Johns Hopkins.
The patient's face will often have a “leonine” appearance. The hands may appear scleroderma-like, with flexion contractures of the fingers. Some patients have microstomia.
Findings from an incisional biopsy will show a distinct infiltrative process with massive amounts of mucin deposition. Patients will have a low-level monoclonal gammopathy, with no specific distribution of subtype. As with most fibrosing skin disorders, punch biopsy is not generally helpful in the diagnosis and is often not necessary.
Aside from the skin, scleromyxedema affects the neurologic, hematologic, gastrointestinal, and cardiopulmonary systems. Neurologic symptoms may include encephalopathy, seizures, stroke, psychosis, aphasia, gait disturbance, vertigo, and tinnitus. Cardiopulmonary involvement includes pulmonary hypertension in approximately 50% of patients, as well as pericardial effusion. Gastrointestinal symptoms can include dysphagia and esophageal dysmotility, Dr. Boin said.
Less commonly, some scleromyxedema patients will experience proximal muscle weakness or frank myopathy, with biopsy showing inflammation, atrophy, necrosis, and mucin deposition.
Without treatment, progressive disease and a poor prognosis are typical. Currently, there is no consistent therapeutic approach and few available long-term data. Treatments that have been investigated in small studies include thalidomide, cyclosporine, autologous stem cell transplants, prednisone, isotretinoin, intravenous immunoglobulin (IVIG), dermabrasion, extracorporeal phototherapy, radiation therapy, plasmapheresis, and psoralen-ultraviolet-light therapy.
Findings from a review of nine scleromyxedema patients who were referred to The Scleroderma Center at Johns Hopkins between 1996 and 2005 showed the mean patient age at diagnosis was 53.6 years (range 33–74), and the mean disease duration prior to referral was 2.1 years (range 0–6). Eight of the patients were white, and one African American. The majority (seven of nine) were female. Monoclonal gammopathy was present in eight patients, but none had evidence of multiple myeloma.
Clinical manifestations mimicking scleroderma included Raynaud's phenomenon in five (another had “cold sensitivity”), sclerodactyly (five), pulmonary hypertension (three), and gastroesophageal reflux disease (two). Encephalopathy was present in one patient, dysphagia in four, elevated creatine phosphokinase in two, and rhabdomyolysis in one. The only autoantibody detected was an antinuclear autoantibody in two patients, Dr. Boin's Hopkins associates Dr. Laura K. Hummers and Dr. Frederick M. Wigley reported in a poster at the 2005 American College of Rheumatology meeting.
Four of the patients with severe symptomatic skin involvement were treated with IVIG at a dose of 2 g/kg daily for 5 days. All patients tolerated the full course of IVIG, and all experienced dramatic improvement in their papular mucinosis skin lesions. Of those four, one also experienced rapid resolution of severe neurologic involvement after just one IVIG course, and another received six monthly treatments and continued without flare 4 months later.
The other two patients, followed for 31 and 34 months, respectively, postinitial treatment, both responded to six monthly treatments, reflared after 4 months, and are now continuing to respond to low-dose infusions at regular intervals—every 4–6 weeks in one patient, every 8 weeks in the other—to maintain control. Indeed, while IVIG appears to produce dramatic and rapid response, with “a softening in a matter of days,” it may be necessary to continue therapy long term, he noted.
One scleromyxedema patient received IVIG 2 g/kg once monthly for 6 months and then every 8 weeks for 1 year. Photos courtesy Dr. Laura Hummers