A Case of a Serum Sickness-Like Reaction After Postexposure Rabies Prophylaxis.

BACKGROUND: Serum sickness secondary to rabies postexposure prophylaxis is not well documented in the medical literature. Our case describes serum sickness after exposure to human-derived rabies immunoglobulin (HRIG) and three human diploid rabies vaccines (HDCV) in a young adult male. CASE REPORT: A 30-year-old previously healthy male patient presented to the Emergency Department with complaints of fever, rash, and jaundice, and had a hospital course complicated by biliary stenosis likely secondary to reactive periportal lymphadenopathy. His initial laboratory values demonstrated obstructive jaundice and slightly elevated complement component 4 levels. These symptoms likely are due to the course of HRIG and HDCV vaccines the patient completed after being exposed to a rabies-positive bat in his home. The patient was hospitalized for 8 days, during which he underwent an endoscopic retrograde cholangiopancreatography with sphincterotomy and biliary stenting. He had one repeat hospitalization for acute blood loss anemia attributed to sphincterotomy, which did not require transfusion or further intervention. Liver biopsy showed cholestatic hepatitis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Medical literature describing serum sickness or a serum sickness-like reaction occurring from exposure to HRIG or HDCV is sparse despite the commonality of postexposure rabies prophylaxis in health care. It is important to educate practitioners on this potential complication and highlight next potential consultations and treatments.

Rituximab-induced serum sickness is more frequent in autoimmune diseases as compared to hematological malignancies: A French nationwide study.

INTRODUCTION: Rituximab induced serum sickness (RISS) is a rare delayed hypersensitivity reaction. The aim of this study was to describe the epidemiological and clinical characteristics of the RISS cases reported in France. METHOD: Serum sickness cases involving rituximab were identified from the French PharmacoVigilance Database from 1998 to 2016. RESULTS: We analyzed 37 cases of RISS. Rituximab was prescribed for an autoimmune disease in 78% of cases. Serum sickness occurred mainly after the first injection (54%) with a median time to onset of 12 days. The most frequent manifestations were rheumatologic symptoms (92%), fever (87%), and skin lesions (78%). The incidence was significantly higher when rituximab was used for autoimmune diseases than for a hematological malignancies. Taking into account the existence of a Systemic Lupus Erythematosus (SLE) as the indication of rituximab or as a comorbidity, the incidence of RISS in patients with SLE was even higher. DISCUSSION: We report on the largest series of RISS studied to date and confirm that this reaction preferentially occurs in patients with autoimmune disease, especially SLE. This may be due to B-cell lysis, leading to the release of intracellular antigens into the serum and subsequent antigen-antibody complex formation, especially in patients with elevated autoantibody production. This could also explain why RISS often occurred after a single injection. CONCLUSION: Patients generally recovered from RISS rapidly without obvious benefit from corticosteroid therapy. The risk of recurrence should prompt clinicians to question the use of rituximab after an episode of RISS.

Successful Treatment of Pemphigus Vulgaris With Ofatumumab

Rituximab is a chimeric anti-CD20 monoclonal antibody that is very effective in treating patients with pemphigus vulgaris. Though infrequent, the development of human anti-chimeric antibodies in patients receiving rituximab results in loss of efficacy. Ofatumumab is a second-generation fully-human anti-CD20 monoclonal antibody currently used to treat chronic lymphocytic leukemia. We report a case of a patient with pemphigus vulgaris successfully treated with ofatumumab after developing human anti-chimeric antibodies to rituximab. J Drugs Dermatol. 2018;17(12):1338-1339.

Rituximab Hypersensitivity: Evaluation, Desensitization, and Potential Mechanisms.

BACKGROUND: Rituximab (Rituxan) hypersensitivity (RITS) can be severe and limits the ability to further administer the treatment. Understanding its pattern and desensitization may permit administration in difficult cases. OBJECTIVE: Analyze RITS patient characteristics, hypersensitivity pattern, and desensitization outcomes to optimize management. METHODS: Twenty-five patients with RITS were referred to the Allergy/Immunology Unit at Massachusetts General Hospital over 5 1/2 years. Their clinical reaction patterns were analyzed. Drug desensitizations were performed using 3 related continuous intravenous protocols that were chosen on the basis of clinical history, skin test reactivity, and the patient's previous desensitization outcomes. RESULTS: Of the 25 referred patients, 23 had lymphoma of various types. The 25 patients underwent 170 continuous intravenous desensitizations based on 3 related protocols, with most based on the intermediate protocol. All but 2 desensitizations were completed successfully. Overall 24% of the desensitizations were complicated by hypersensitivity reactions. Two patients with serum sickness and a patient with mast cell disorder were also successfully managed. The average hypersensitivity reaction grade was 3.0 (2-4) before desensitization and 0.41 with desensitization. Skin tests were performed in 18 patients, with 5 patients positive initially and 2 more converted from negative to positive. Skin test status was not helpful for risk stratification for hypersensitivity reactions. Tryptase level was elevated during 21% of desensitizations with reactions but rare among asymptomatic desensitizations. CONCLUSIONS: Nearly all patients with severe sensitivity to rituximab can be successfully desensitized. IgE-mediated mechanism and mast cell degranulation, in addition to cytokine release syndrome and tumor lysis syndrome, may contribute to a significant portion of hypersensitivity reactions among patients with RITS.

Serum sepsis, not sickness.

Rarely taught in medical schools, clinical reasoning is the ability to discern the important from the unimportant and to arrive at accurate and efficient clinical conclusions. Identifying errors in reasoning is difficult; however, undetected clinical reasoning errors can have exponential consequences. As quality and patient safety come into focus, identifying and preventing clinical reasoning errors have become imperative. The authors present a case of a man sent for admission from a subspecialty clinic diagnosed with infliximab-induced serum sickness. Not countering the expert's diagnosis, initial workup failed to diagnose joint abscess and sepsis. Heuristics are mental shortcuts used to make decision making more efficient but can lead to error. The anchoring heuristic, premature closure, confirmation bias and the blind obedience heuristic are examples. Introspective surveillance and interactive hypothesis testing defend against heuristics. The authors conclude by discussing 4 types of hypersensitivity reactions, serum sickness in particular, and the chimeric nature of infliximab.

Serum sickness-like syndrome after immunoglobulin M-enriched polyclonal immunoglobulin.

Medication reactions, infectious etiologies, graft vs. host disease, serum sickness, and serum sickness-like reaction are the most common conditions that cause skin fever and rashes in immunosuppressed patients. In addition to this long list of diseases, severity of the primary disease and deterioration in the patient's health status can make the diagnosis difficult. Furthermore, cutaneous and histological similarities in these mentioned conditions can be confounding. Here, we present a 16-year-old male patient with acute myeloid leukemia suffering from skin rashes and fever that appeared following a chemotherapy course leading to bone marrow suppression. We aim to discuss the differential diagnosis and share the diagnostic challenges that we already have experienced after immunoglobulin M-enriched polyclonal immunoglobulin.

[Serum sickness induced by rituximab infusion; report of two cases with hematological malignancies].

We report 2 cases of serum sickness after rituximab infusion. Case 1 is a patient with Waldenström's macroglobulinemia, and case 2 is a patient with marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and Sjögren's syndrome. Both patients had polyclonal hypergammaglobulinemia, were treated with rituximab monotherapy, developed serum sickness between 9 and 17 days after the first rituximab infusion, developed fever and arthralgia, and improved soon after corticosteroid treatment. Serum sickness after rituximab treatment for hematological malignancies is very rare as far as we know. We identified three risk factors of serum sickness after rituximab infusion from previous reports and our cases; administration of rituximab alone, the existence of Sjögren's syndrome, and polyclonal hypergammaglobulinemia.

Transfusion-induced serum sickness.

BACKGROUND: Transfusion-induced serum sickness reactions are rarely reported in the literature. The Type III hypersensitivity reaction to heterologous proteins involves deposition of complement and immune complexes in small vessel walls resulting in a leukocytoclastic vasculitis. A case of a multiply transfused patient with several episodes of serum sickness reactions is presented. CASE REPORT: A 61-year-old man with myelodysplastic syndrome type refractory anemia presented with fever, rash, and polyarthralgia 5 days after transfusion of red blood cells (RBCs). By transfusing plasma-free "washed" RBCs, similar serum sickness reactions were avoided. RESULTS: Laboratory investigation showed an increase of serum creatinine, hematuria, and proteinuria. Levels of circulating immune complexes immunoglobulin G and immunoglobulin M were increased. Hypocomplementemia could not be demonstrated. Histopathologic examination of the skin showed leukocytoclastic vasculitis, compatible with serum sickness. CONCLUSION: The importance of early recognition of transfusion-induced serum sickness reactions is emphasized, because this can reduce unnecessary morbidity from this unusual complication of transfusion. To prevent this type of transfusion reaction, patients who experienced serum sickness-like reactions after transfusion should only receive plasma-free washed RBCs.

Combining systemic retinoids with biologic agents for moderate to severe psoriasis.

BACKGROUND: Moderate to severe psoriasis, which is defined as psoriasis affecting more than 20% of the body surface area, often requires a combination of therapies to achieve remission. Although numerous data exist regarding the use of acitretin and biologic agent therapy alone for psoriasis, little is known about the efficacy, safety, and tolerability of acitretin combined with biologic agents. METHODS: Fifteen patients with psoriasis treated with concomitant acitretin and a biologic agent were identified, and their charts were reviewed for response to therapy, additional therapy necessary for disease management, side-effects, and laboratory abnormalities whilst on combination therapy. The Institutional Review Board did not require approval for this chart review. RESULTS: Twenty-nine per cent of patients showed clearance of psoriasis, 43% of patients showed an improvement of 90%, 14% showed an improvement of 75%, and 7.1% showed no change. During treatment with acitretin and biologic agent, five patients required no adjunctive treatment. Three patients were able to stop narrow-band ultraviolet-B (UV-B) therapy after an average of 2.33 months of combination therapy. Only one patient continued to require phototherapy (UV-B) in addition to the biologic agent. Three patients developed squamous cell carcinoma (SCC) whilst on combination therapy, but all patients had a previous history of SCC. One patient developed non-Hodgkin's lymphoma after 3 years of etanercept and acitretin, and the etanercept was discontinued. CONCLUSIONS: Acitretin combined with biologic agents offers a promising method of managing refractory psoriasis. More research is needed to determine the long-term safety and efficacy of this combination.

Serum sickness in a patient with follicular lymphoma after rituximab and radioimmunotherapy with ibritumomab tiuxetan.

A previously healthy 47-year-old woman was treated for follicular lymphoma, grade III, with cyclophosphamide, adriamycin, vincristine, prednisone with rituximab (CHOP-R) followed by ibritumomab tiuxetan and rituximab. She developed a serum sickness-like illness during immunotherapy with fever, myalgias, arthralgias, and pleural and pericardial effusions. Despite anti-inflammatory therapies her symptoms persisted for 10 months before ultimate resolution. Her clinical course and literature are reviewed.

Serum sickness-like reactions in patients receiving intravenous infliximab.

Infliximab, a monoclonal antibody against tumor necrosis factor (TNF) has been used successfully for the treatment of certain forms of Crohn's disease and rheumatoid arthritis. Both acute and delayed hypersensitivity reactions have been associated with the intravenous use of this drug. The delayed forms may present as a serum sickness-like illness and recognition of the clinical manifestations becomes crucial for early diagnosis and treatment. With the dramatic increase in the use of infliximab, there will likely be increased numbers of patients with this type of reaction. These patients may have received this drug days or even weeks before the clinical presentation. These types of reactions also have been reported with the use of other monoclonal antibodies.

Infliximab-induced headache and infliximab-induced meningitis: two ends of the same spectrum?

This report describes a case of aseptic meningitis induced by the tumor necrosis factor-alpha inhibitor infliximab. The patient, a 51-year-old female, was being treated for Crohn's disease. After an infliximab infusion, she had headache, fever, arthralgia, myalgia, and meningismus. Cerebrospinal fluid analysis was remarkable for a neutrophilic pleocytosis and elevated protein. Other potential causes of meningitis were excluded. Her symptoms completely resolved within 24 hours of presentation. Because infliximab commonly causes headache and is very immunogenic, we infer that infliximab-induced meningitis is immune-mediated and underrecognized. Potential risk factors and means for minimizing its occurrence are offered.

Safety aspects of infliximab in inflammatory bowel disease patients. A retrospective cohort study in 100 patients of a German University Hospital.

BACKGROUND: Infliximab, a chimeric anti-tumour necrosis factor monoclonal antibody with potent anti-inflammatory effects, represents an effective treatment option in patients with severe inflammatory bowel disease (IBD). Serious side-effects of such an immunomodulating therapy are speculated and therefore we reviewed our clinical experience in a retrospective safety study looking upon a single cohort of 100 IBD patients from a large German University Hospital. METHODS: 100 patients with severe Crohn's disease (n = 92), ulcerative colitis (n = 7) or indeterminate colitis (n = 1) treated with infliximab (5 mg/kg) from January 2000 to December 2003 were retrospectively analysed for acute and subacute adverse events by chart review. RESULTS: Overall, infliximab therapy was generally well tolerated. No fatal complications, malignancies, autoimmune diseases, neurologic or cardiovascular complications were observed in the cohort during the study period. Overall, adverse events were observed in 10 patients: 2 patients showed an acute infusion reaction, 1 patient a serum sickness-like reaction, in 4 patients a bacterial or viral infection occurred, in 1 patient pancytopenia and 2 patients developed surgical complications. Only 6 patients with adverse events required admission to hospital. A case of tuberculosis after infliximab was not found. The lack of adverse side-effects was associated with young median age and infrequent comorbidities of the cohort. CONCLUSION: Regarding its strong immunomodulating capacity, infliximab appears to be an efficient and relatively safe therapeutic option for patients with severe IBD. However, the use of infliximab requires careful screening and close patient monitoring to identify patients at risk and the infrequent, but sometimes serious complications of infliximab.

Infliximab therapy in Crohn's disease: safety issues.

Infliximab has become a valuable addition to the therapeutic arsenal for Crohn's disease. Although the rate of adverse events was relatively low in the premarketing trials, several investigators have recently reported experience in large groups of patients. This has shed more light on safety aspects of infliximab therapy, which should change the approach towards patients prior to infliximab infusion. This review discusses some immunological aspects that are relevant for infliximab therapy and provides guidelines for daily practice.

Serum sickness-like syndrome due to mosquito bite.

Local inflammatory reactions at the site of a mosquito bite are frequent. Immediate systemic reactions have occasionally been reported. The first case of a patient with relapsing episodes of a serum sickness-like syndrome following mosquito bites is reported herein. A 62-year-old patient came to the emergency room complaining of sudden malaise, chills, fever, headache, cervical lymph node enlargement, arthromyalgia, generalized purpura and leukopenia 6 h after a mosquito bite. He had experienced multiple similar episodes in the last 20 years, also following mosquito bites. Infectious and autoimmune diseases were ruled out. Serum IgE was 9,102 kU/l. Prick test of whole-body Culex pipiens extract was positive. Specific IgE to Aedes communis was 2.25 kU/l. SDS-PAGE immunoblotting of the patient's serum with whole-body C. pipiens extract revealed 43 and 17 kDa IgG-binding proteins and 22 and 17 kDa IgE-binding proteins, neither of which were found with control sera. Skin biopsy was consistent with leukocytoclastic vasculitis. The presence of both mosquito-specific IgE and IgG in the patient's serum suggest a possible cooperative immune response leading to clinical manifestations of serum sickness.

[Glomerulonephritis caused by acute serum sickness]. / Glomerulonefritis door acute serumziekte.

A 51-year-old male patient was treated for a rejection episode after kidney transplantation with horse antithymocyte globulin (ATG). Twelve days after the start of the ATG treatment he developed fever, arthralgia, purpura and acute renal failure. This clinical picture is characteristic of serum sickness, resulting from formation of antibodies to a foreign protein and development of immune complexes. Kidney biopsy revealed an endocapillary glomerulonephritis. Immune complexes probably develop in the mesangium and along the glomerular basal membrane through local formation and precipitation from the circulation. Spontaneous recovery is the rule.