Serum sickness reaction to obinutuzumab in a patient with chronic lymphocytic leukaemia.

Serum sickness (SS) is a known phenomenon; however, it is commonly missed due to vague symptoms, and is usually confounded by other aetiologies that present similarly. Obinutuzumab is a novel anti-CD20 antibody agent that has been approved for chronic lymphocytic leukaemia (CLL) treatment. At the time of approval, it was not linked to SS; however, this phenomenon has been recognised with other anti-CD20 agents like rituximab. SS remains a rare entity, but it is important to be recognised accurately and quickly in the appropriate circumstances, so that effective treatment with corticosteroids can be initiated to alleviate inflammatory symptoms. Here we present a patient with CLL who developed maculopapular rash, fever and polyarthritis and elevated inflammatory markers consistent with serum sickness triggered by obinutuzumab and was effectively treated with corticosteroids.

Serum sickness induced by alemtuzumab in a kidney-pancreas transplant recipient.

Serum sickness is an immune-complex-mediated hypersensitivity reaction that was first noted in the early 1900s in patients receiving heterologous antisera, such as horse antitetanus or antidiphtheria serum. This condition is primarily self-limited; however, in its acute state, it can cause severe symptoms of fever, rash, polyarthritis, or polyarthralgias. In solid organ transplantation, this condition is frequently reported in association with the use of rabbit anti-thymocyte globulin and chimeric murine monoclonal antibodies such as rituximab. Alemtuzumab, designed as a humanized monoclonal antibody against CD52, is expected to be less immunogenic. Here, we report a case of serum sickness associated with alemtuzumab induction therapy in a kidney-pancreas dual-organ recipient.

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.

Efficacy and safety of etanercept for postoperative pyoderma gangrenosum after infliximab serum sickness.

Non-peristomal postoperative pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that occurs in the early postoperative period at surgical incisions, most commonly after breast surgery. Early diagnosis and treatment is essential to prevent severe scaring. TNF-alpha inhibitor infliximab was reported to be efficient in treatment of PPG refractory to systemic corticosteroids. However infliximab can be not well tolerated. We report the first case of etanercept efficacy in post-plastic breast surgery pyoderma gangrenosum after infliximab serum sickness.

Urticaria mimickers in children.

Acute urticaria is a self-limited cutaneous condition marked by transient, erythematous, and pruritic wheals. It is a hypersensitivity response that is often secondary to infection, medications, or food allergies in children. In contrast, the urticarial "mimickers" described in this review article are often seen in the context of fever and extracutaneous manifestations in pediatric patients. The differential diagnosis ranges from benign and self-limited hypersensitivity responses to multisystem inflammatory diseases. Establishing the correct diagnosis of an urticarial rash in a pediatric patient is necessary to both prevent an unnecessary work up for self-limited conditions and to appropriately recognize and evaluate multisystem inflammatory disorders. Herein, we describe two cases to illustrate the clinical manifestations, laboratory findings, histopathology and differential diagnoses for several mimickers of acute urticaria including: urticaria multiforme, serum sickness like reaction, Henoch-Schönlein purpura, acute hemorrhagic edema of infancy, systemic onset juvenile idiopathic arthritis, cryopyrin associated periodic syndromes, and urticarial vasculitis.

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 and severe acute renal failure after rabbit antithymocyte globulin treatment in aplastic anemia: a case report.

Serum sickness is an immune-complex-mediated illness that frequently occurs in patients after polyclonal antibody therapy (thymoglobulin). Although serum sickness has been described secondary to thymoglobulin therapy in adults, there are no reports in children on thymoglobulin-induced acute renal failure. We report a case of serum sickness in a 10-year-old girl who was treated for severe aplastic anemia using rabbit antithymocyte globulin (ATG). Eleven days after being started on antithymocyte globulin treatment, she developed fever, gross hematuria, arthralgia, rash, and acute renal failure. Laboratory results showed decreased complement levels, hypergammaglobulinemia, serum creatinine of 4.8 mg/dL (0.6 mg/dL at baseline), and blood urea nitrogen of 79 mg/dL (28 mg/dL at baseline). Peritoneal dialysis was required for 14 days. The patient's symptoms resolved after 13 days on treatment with a short course of high-dose steroids for 3 days, followed by a prednisolone taper. Early recognition and accurate diagnosis is the key for managing thymoglobulin-induced serum sickness, as treatment is highly effective at achieving good outcomes.

A four-year-old boy with fever, rash, and arthritis.

The triad of fever, rash, and arthritis in a hospitalized child suggests an inflammatory, infectious, or postinfectious process in most cases; however, malignancy must be considered. The most common causes in this age group are inflammatory conditions, including Kawasaki disease, Henoch-Schönlein Purpura, serum sickness-like reaction, and juvenile idiopathic arthritis. Other rarer inflammatory processes can present with this triad of symptoms such as Cryopyrin-related diseases (autoinflammatory disorders), urticarial vasculitis, and systemic lupus erythematosus. We will discuss the differential diagnosis and inpatient management of fever, rash, and arthritis in a young child, focusing on inflammatory conditions. The important features which can help distinguish these conditions include the nature of the rash, associated signs or symptoms, time course of the eruption, and characteristic laboratory and/or histologic findings.

Serum sickness-like reaction associated with cefazolin.

BACKGROUND: Although 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 PRESENTATION: A 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. CONCLUSION: Serum sickness-like reaction may be associated with cefazolin therapy.

Pediatric bupropion-induced serum sicknesslike reaction.

This reports the first 2 cases of serum sicknesslike reaction to bupropion in children (age 12 and 14). Serum sicknesslike reactions are an example of immune-complex medicated disease. The cardinal symptoms of serum sickness are fever, lymphadenopathy, arthralgias or arthritis, and urticaria. Symptoms usually resolve without long-term sequela following discontinuation of the exogenous antigen. It is likely that serum sicknesslike reactions to bupropion are either relatively rare or underrecognized and underreported. Between May 1998 and May 2001, GlaxoSmith Kline received 172 reports of seizures (a well-known adverse drug reaction) and only 37 reports of serum sicknesslike reactions (Wooltorton 2002). We do not know if children and adolescents are more prone than adults to develop serum sicknesslike reactions to bupropion. Luckily, the reported cases of serum sicknesslike reactions to bupropion have not caused irreversible morbidity or mortality. Nevertheless, the symptoms are painful, temporarily disfiguring and disabling, and warrant prompt medical attention. Parents and patients should be educated about this potential side effect at the onset of treatment, because symptoms are similar to many infectious childhood illnesses, and the treatment of serum sicknesslike reactions to bupropion should include the discontinuation of bupropion.

[Febrile toxiderma in children]. / Toxidermies fébriles de l'enfant.

Febrile cutaneous drug reactions in the child represent 6% of paediatric hospitalizations for dermatologic reasons. Diagnosis is difficult, for both infectious diseases and drug allergy can induce the same skin reaction. The same eruption can correspond to several drug-induced reactions. In a single child, there may be several causes of skin eruption and several drugs inducing similar cutaneous reactions. Clinical diagnosis and the method of clinical imputability lead to diagnosis. Paraclinical methods are of limited interest. Symptomatic treatment is begun on emergency admission. Upon identification, the responsible drug can be withheld and the authorities responsible for post-marketing surveillance can be notified.

[Lymphadenopathies and diseases with manifestations of autoimmunity]. / Linfoadenopatie e malattie con manifestazioni di autoimmunità.

The diseases responsible for lymphadenopathies with autoimmune features were examined. Such features play a major role in a vast number of clinical conditions whose aetiology is for the most part unknown but which present several clinical, histological and laboratory aspects in common. The most significant of these conditions are serum sickness and similar pictures induced by drugs, iodised contrast media and hymenoptera venom, angioimmunoblastic lymphadenopathies, giant multicentric lymph node hyperplasia, diffuse connectivitis, Wegener's granulomatosis lymphoid granulomatosis, necrotic lymphadenitis without granulocyte infiltration, mucocutaneous lymph node syndrome, angiofollicular hyperplasia with eosinophilia and histiocytosis of the sinuses. In some of these conditions, the lymphadenopathy is a constant and characteristic feature of the disease; in others it is common, in others rare and at time purely local. The autoimmune changes encountered in these conditions may, at times, be responsible for the morbidity, as in serum sickness. In others they merely constitute major or minor symptoms. In some they are no more than marginal aspects. The onset is usually acute with widespread symptoms and a clinical control featuring manifestations of hypersensitivity and immune deficiency. The most common and characteristic laboratory findings are polyclonal hypergammaglobulinaemia, circulating immune complexes, cryoglobulinemia and hypocomplementaemia and finally medullary plasmocytosis. Lymph node biopsy also tends to reveal a standard picture characterised by polymorphic infiltration of immunologically normal cells and the proliferation of newly formed small calibre blood vessels, mostly venules: In other words an aspecific reactive picture. For this reason diagnosis will sometimes be provided by blood tests, sometimes by repeated biopsy at a later date, sometimes by the evolution of the clinical picture. One other feature of these conditions and common, incidentally, to almost all diseases involving immunological alterations, is that they may be complicated by the appearance of lymphomas. Among the diseases quoted particular attention was paid to angioimmunoblastic lymphadenopathy and Castleman's disease given their greater frequency and the importance of their aetiopathogenic and clinical aspects.

Disorders that mimic CNS infections.

A variety of inflammatory and neoplastic disorders can cause signs, symptoms, and laboratory abnormalities suggesting CNS infection. The distinction usually can be made through careful consideration of the entire clinical picture and the judicious use of additional laboratory tests.

Rapid serologic diagnosis of serum sickness from antithymocyte globulin therapy using enzyme immunoassay.

Although the use of antithymocyte globulin/antilymphocyte serum (ATG/ALS) has been shown to be beneficial in treating renal allograft rejection, the incidence and nature of serum sickness reactions following such treatment have received limited attention. In the setting of rejection or infection, the diagnosis of serum sickness is often difficult on clinical grounds, and biopsy may be an undesirable means of obtaining documentation. A sensitive enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies against ATGAM (Upjohn) and was utilized in 35 patients treated for rejection with ATGAM following clinical unresponsiveness to bolus methylprednisolone therapy. Serum sickness was diagnosed clinically in 7 of these patients (20%) during or immediately following ATGAM therapy. Significant titers of anti-ATGAM antibody were found in these 7 cases, as well as 5 additional cases (14%). Upon retrospective review, the diagnosis of serum sickness was also made in each of these 5 additional cases based upon the immunopathologic detection of horse immunoglobulin deposits in vessels of tissue (lung or kidney) examined. In 2 other cases where serologic testing was negative, there was some clinical suggestion of serum sickness that could not be documented pathologically. ELISA for anti-ATGAM antibodies was negative in testing 46 control patients and pooled normal sera. In one case, retrospective testing of pre-ATGAM therapy serum samples showed significant antihorse antibodies. Despite a negative skin test prior to administration, this patient developed symptoms of serum sickness 15 days after the onset of ATGAM therapy. Extremely high titers of antibody were detected 5 days earlier (10 days posttherapy), and the presence of horse immunoglobulin immune complexes in the kidney was documented following graft loss that occurred within 4 weeks. These findings indicate (1) serologic testing for anti-ATGAM antibodies using a sensitive ELISA method provides a quick, inexpensive, noninvasive means for the presumptive diagnosis of serum sickness in complicated clinical situations, and (2) screening of patient sera prior to administration of ATGAM may be useful in avoiding potential serum sickness reactions.