Intravenous Immunoglobulin–Induced Hemolytic Anemia in a Patient With Juvenile Dermatomyositis

Dermatomyositis (DM) is an inflammatory myopathy defined by progressive weakness and classically associated with a heliotrope or violaceous rash, Gottron sign, and periungual erythema.^1,2 Juvenile DM presents before the age of 18 years and is distinct from its adult counterpart.^3,4 Dermatologic involvement may range from mild photosensitivity to generalized rash with systemic vasculitis.^1,2 Histopathology derives from immune complex–mediated, complement-dependent attack of the vascular endothelium, resulting in marked loss of muscle capillaries.¹

Therapy for juvenile DM is aimed to prevent or slow progression of irreversible myopathic damage, since one-third of patients will improve in 2 to 3 years.⁵ While oral or intravenous (IV) pulse corticosteroids with or without methotrexate and azathioprine is the treatment of choice, high-dose intravenous immunoglobulin (IVIG) has been used for steroid-sparing effects.⁶ In a double-blind, placebo-controlled, randomized crossover study, Dalakas et al demonstrated the efficacy of IVIG for DM.⁷ Of 12 patients treated with IVIG (1 g/kg for 2 days, then monthly for 3 months), 9 showed drastic clinical improvement. Whereas, of 11 patients in the placebo arm, 3 had mild improvement, 3 had no change, and 5 had worsening of their condition.⁷ Although adverse effects may occur in more than one-third of autoimmune disease patients treated with IVIG, they are usually minor and most commonly include headache, flushing, chills, myalgia, wheezing, tachycardia, lower back pain, and nausea.⁸

IVIG acts to inhibit humoral effector mechanisms. One such proposed mechanism of action is the competitive blockade of Fc receptors on reticuloendothelial cells.⁹ Other studies have suggested that IVIG may modulate antibody production and cytokine trafficking.¹⁰ However, specific to DM, Basta and Dalakas proposed that IVIG prevents endothelial injury and consequent intramuscular capillary damage by interfering with antibody-dependent formation of the C5-9 membrane attack complex (MAC).¹¹ In another study, using a model of Forssman shock in animal models, Basta proposed that the efficacy of IVIG in DM may be attributed to covalent and noncovalent interaction with activated C3 (C3b) and C4 (C4b) components,¹² thereby preventing MAC formation.

An 11-year-old Caucasian female presented with fever, severe weakness, and myalgia predominantly affecting the bilateral deltoids, triceps, iliopsoas, and anterior tibial muscles that had progressively increased over the past weeks. Gottron sign and heliotrope rash were noted on physical examination. Subsequent muscle biopsy of the left biceps demonstrated considerable variability in muscle fiber size and rare foci of centralization and nuclei with a marked lymphoplasmacytic interstitial inflammatory infiltrate and scattered fibrogenesis, suggestive of DM. Serum creatine kinase (CK) level at initial presentation was 11,000 U/L. Anti-SSA/Ro titers were positive, while titers of antinuclear antibody, rheumatoid factor, anti-SSB/La, antineutrophil cytoplastic antibodies, and Jo-1 antibodies were negative. C3 and C4 complement levels were within the normal range. Serum electrophoresis showed polyclonal gammopathy, and serum IgA was found to be within normal range. At the time of diagnosis, prednisone therapy was initiated at 1 mg/kg and tapered to 3 mg/kg over a 3-week period. At the end of 3 weeks, the patient continued to require assistance when walking and was unable to stand from a sitting position without assistance. Therefore, azathioprine therapy at 50 mg/day was added to the treatment plan. When reevaluated 1 week later, the patient continued to have persistent weakness and similar physical findings, prompting admission for a 5-day course of IVIG (55 g/kg; Polygam; Baxter Healthcare Corporation, Deerfield, IL). Baseline hemoglobin level of 15 g/dL was recorded immediately before starting IVIG therapy, and at the conclusion of IVIG administration, the patient experienced drastic clinical improvement and was stable for discharge.

Four days later, the patient returned to the hospital with acute-onset headache, shortness of breath, low-grade fever (37.8°C),