Israel Medical Association Journal

Scleromyxedema is a rare, chronic cutaneous mucinosis characterized clinically by diffuse indurated plaques, numerous waxy papules, and potential for systemic involvement, including neurological, pulmonary, and gastrointestinal complications. It can significantly impact the clinical course and patient prognosis [1].

Histologically, scleromyxedema typically manifests in two main forms. The classic form, the most common variant, is characterized by dense mucin deposition within the dermis, an increase in fibroblasts, and thickened collagen. The granuloma annulare-like variant, accounting for approximately 23% of cases, mimics granuloma annulare and is characterized by interstitial granulomatous infiltration and, in some cases, palisaded granulomas within the dermis. This unusual variant presents a significant diagnostic challenge due to its overlap with other granulomatous conditions, potentially causing diagnostic delays [2].

The lack of standardized treatment regimens makes managing scleromyxedema complex. Intravenous immunoglobulin (IVIG) has emerged as a leading therapeutic option, demonstrating efficacy in controlling both cutaneous and systemic manifestations. Other options include systemic steroids, thalidomide, retinoids, and melphalan [3].

These cases underscore the challenges of recognizing the clinical and histologic variability of scleromyxedema, which may lead to a delay in the diagnosis. Early diagnosis is critical given the potential for systemic involvement (neurological, gastrointestinal, and muscular) and the association of scleromyxedema with monoclonal gammopathy of undetermined significance (MGUS), which might progress to multiple myeloma. Consequently, timely hematologic evaluation and ongoing surveillance are warranted.

Background: Guillain-Barré syndrome (GBS) is an autoimmune disease of the peripheral nervous system with a typical presentation of acute paralysis and hyporeflexia. Intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) are treatments that have proven to expedite recuperation and recovery of motor function.

Objectives: To describe our experience at one tertiary medical center treating GBS with IVIG and to compare the efficacy of IVIG as the sole treatment versus combined therapy of IVIG and plasma exchange.

Methods: We reviewed the records of all patients diagnosed with GBS and treated with IVIG at the Sheba Medical Center from 2007 to 2015 and collected data on patient demographics, disease onset and presentation, and treatments delivered. The motor disability grading scale (MDGS) was used to evaluate the motor function of each patient through the various stages of the disease and following therapy.

Results: MDGS improvement from admission until discharge was statistically significant (P < 0.001), as was the regainment of motor functions at 3 and 12 months follow-up compared to the status during the nadir of the disease. The effectiveness of second-line treatment with IVIG following PLEX failure and vice versa was not statistically significant (P > 0.15).

Conclusions: The majority of patients included in this study experienced a significant and rapid improvement of GBS following treatment with IVIG. Combined therapy of PLEX and IVIG was not proven to be effective in patients who encountered a failure of the first-line treatment.

Background: Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunogIobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG).

Objectives: To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination.

Methods: Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCl and 0.01 M phosphate-buffered saline (PBS), pH 7.4, with or without a further twofold dilution in a low ionic strength solution.

Results: A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations.

Conclusions: Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism.