Serum Sickness

BackgroundAlthough rare, serum sickness-like reactions have been documented to occur following the administration of many antibiotics. Cefazolin, a first generation cephalosporin, is a commonly prescribed antibiotic which is considered to be generally safe and well tolerated. There have been no prior reports linking this drug with sickness-like reactions. We report a probable case of serum sickness-like reaction following a single dose of cefazolin.Case presentationA 23 year old man with no significant past medical history was admitted to undergo a laparoscopic donor nephrectomy as part of a living-related renal transplant. One gram of intravenous cefazolin was administered perioperatively. The surgery was completed without complication and the remainder of his hospital course was uneventful. Ten days following discharge the patient developed fevers, painful and swollen joints, and a cutaneous eruption overlying his trunk and extremities. There was no evidence of systemic vasculitis. These clinical findings were most consistent with a serum sickness-like reaction. A brief course of corticosteroids and antihistaminergic therapy was initiated, and complete resolution of the patient's symptoms followed. The Naranjo probability scale indicated that this adverse drug event was probable.ConclusionSerum sickness-like reaction may be associated with cefazolin therapy.

Management of refractory immune thrombocytopenia frequently involves rituximab, a chimeric anti-CD20 monoclonal antibody, to target B cells and induce remission in most patients. However, neutralizing antibodies to rituximab that nullify therapeutic response and may lead to serum sickness have been rarely reported. Here, we present a case of a young adult woman with Evans syndrome treated with rituximab, complicated by the development of serum sickness, acute respiratory distress syndrome, and platelet refractoriness presumed secondary to neutralizing antibodies to rituximab. She was successfully treated with the humanized anti-CD20 monoclonal antibody, obinutuzumab, with subsequent symptom resolution. Additionally, a review of 10 previously published cases of serum-sickness associated with the use of rituximab for idiopathic thrombocytopenic purpura (ITP) is summarized. This case highlights that recognition of more subtle or rare symptoms of rituximab-induced serum sickness is important to facilitate rapid intervention.

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.

RationaleAntivenom is the key specific treatment for clinically significant snakebite envenoming. Delayed serum sickness-like reactions after antivenom therapy may be overlooked after discharge and can resemble infection or septic shock.Patient concernsA woman in her early 60s returned approximately 7 days after antivenom therapy with generalized urticarial and purpuric maculopapular rash, pruritus, fever, vomiting, fatigue, dizziness, hypotension, and thrombocytopenia.DiagnosesThe patient was initially managed for suspected sepsis and septic shock because of circulatory instability, elevated high-sensitivity C-reactive protein, elevated serum amyloid A, elevated procalcitonin, and inflammatory changes on chest computed tomography. The timing after antivenom exposure, rash pattern, decreased complement C3 and C4, proteinuria, and subsequent clinical course supported a severe delayed serum sickness-like reaction as an important contributor. Infection could not be completely excluded because systematic pathogen testing was not completed during the acute phase.InterventionsThe patient received empirical anti-infective therapy, vasopressor support, fluid resuscitation, hydrocortisone, ebastine, albumin supplementation, and other supportive care.OutcomesAfter 7 days of treatment, blood pressure stabilized, rash and pruritus largely resolved, platelet count and inflammatory markers improved, and follow-up laboratory findings showed substantial recovery.LessonsDelayed antivenom-related serum sickness-like reactions may mimic septic shock and may be accompanied by elevated procalcitonin. In patients who develop rash and hypotension within days after antivenom therapy, clinicians should treat possible sepsis promptly while reassessing antivenom exposure, skin findings, complement levels, urinalysis, microbiological evidence, and treatment response.