The case of Kawasaki disease after rituximab infusion triggered by human anti-chimeric antibodies.

Rituximab (RTX) is an effective treatment for refractory nephrotic syndrome (NS), but may produce human anti-chimeric antibodies (HACA) which can cause severe infusion reaction or rituximab-induced serum sickness (RISS). RISS presents with a fever, rash, and arthralgia, which typically occurs 7-21 days after RTX infusion. On the other hand, Kawasaki disease (KD) also presents with fever and rash. There have been no reports of KD developed after RTX infusion. A 6-year-old girl with frequently relapsing NS was admitted to our hospital for fever and rash on day 7 after receiving RTX. Although it was suggestive of RISS at first, she also had conjunctival hyperemia, swelling, and erythema of the hands and feet, and a right coronary artery abnormality on echocardiography. Her symptoms met the diagnostic criteria of KD. We administered intravenous immunoglobulin (IVIg) (2 g/kg), and her symptoms resolved within a few days. The HACA titer determined using the serum collected at admission was very high. This is the first report of KD with a clinical course similar to RISS. It should be noted that a careful follow-up of coronary arteries should be performed in patients suspected of RISS.

Serum sickness-like drug reaction: two cases with a neutrophilic urticarial pattern.

The diagnosis of serum sickness-like reaction (SSLR) is typically based on clinical findings. Histopathologic examination is often deferred, as these eruptions commonly present in young children, and often to primary care providers. A PubMed literature search revealed only five existing cases of SSLR which describe cutaneous histopathologic features. We report two cases of SSLR, one each to bupropion and cefazolin. Skin biopsy findings in both cases showed a neutrophil-predominant urticarial pattern resembling neutrophilic urticaria or neutrophilic urticarial dermatosis. We also provide a summary of the histopathologic findings that can help support a diagnosis of SSLR.

Clinical features of serum sickness after Australian snake antivenom.

Serum sickness is a delayed immune reaction in which the immune system responds to a protein in antiserum as a potentially harmful substance and mounts an IgG-mediated antibody response. A 32 year-old female patient had systemic envenoming following a bite by a red-bellied black snake (Pseudechis porphyriacus). She was treated with Tiger snake antivenom and recovered over 24 h and did not develop myotoxicity. She then presented with local pain, itching and swelling, which was partially treated with antihistamines. Eleven days after the bite she presented again with symptoms of worsening serum sickness including rash on the upper legs, joint and muscle pain in arms, ankles and knees, and nausea. The patient was prescribed five days of prednisone 50 mg/day, antihistamine 10 mg/day and analgesia 1000 mg/day and improved over 2 days. She had no further problems on follow up at 4 months. This case highlights that serum sickness can cause significant effects after the treatment of snake envenoming. It develops 5-14 days after antivenom administration and has characteristic clinical and laboratory features. Severe cases of serum sickness can result in morbidity but it appears to respond well to corticosteroid treatment.

The C5a receptor has a key role in immune complex glomerulonephritis in complement factor H-deficient mice.

Chronic serum sickness leads to the formation of glomerular immune complexes; however, C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CFH) is absent from the plasma. Here we studied the role for C5a receptor (R) in this setting. The exaggerated humoral immune response in CFH(-/-) mice was normalized in CFH(-/-)C5aR(-/-) double knockout mice, highlighting the C5aR dependence. The CFH knockout mice developed proliferative glomerulonephritis with endocapillary F4/80+ macrophage infiltration, a process reduced in the double knockout mice. There was no interstitial inflammation by histologic criteria or flow cytometry for F4/80+ Ly6C(hi)CCR2(hi) inflammatory macrophages. There were, however, more interstitial CD3+ CD4+ T lymphocytes in CFH knockout mice with chronic serum sickness, while double knockout mice had greater than 5-fold more Ly6C(lo)CCR2(lo) anti-inflammatory macrophages compared to the CFH knockout mice. Mice lacking C5aR were significantly protected from functional renal disease as assessed by blood urea nitrogen levels. Thus, IgG- and iC3b-containing immune complexes are not inflammatory in C57BL/6 mice. Yet when these mice lack CFH, sufficient C3b persists in glomeruli to generate C5a and activate C5aR.

A circadian clock in murine bone marrow-derived mast cells modulates IgE-dependent activation in vitro.

Circadian rhythm is expressed in most organisms, and many functions and parameters in the immune system are associated with time-of-day. However, it is largely unknown if local circadian clocks in immune cells directly control physiological outcomes. We hypothesized that a circadian clock in murine bone marrow derived mast cells (BMMCs) modulates IgE-dependent activation in vitro. Mature BMMCs, grown from bone marrow of C57BL/6 mice, were synchronized with serum rich media (50% horse serum). Total RNA was harvested from BMMCs at 4 h intervals for up to 72 h following synchronization and expression of circadian genes (mPer1, mPer2, Bmal1, Rev-erbα, and Dbp) was measured by quantitative PCR. Serum shock synchronized expression of circadian genes (mPer2, Bmal1, Rev-erbα, and Dbp) in BMMCs. Synchronized BMMCs stimulated via the high affinity IgE receptor (FcεRI) at different time intervals display circadian rhythms in IL-13 and IL-6 mRNA expression. The expression of fcer1a gene and FcεRIα protein displayed a circadian pattern following serum shock, with mean periods of 18.9 and 28.6 h, respectively. These results demonstrate that synchronized BMMCs provide an in vitro model to study circadian mechanism(s) associated with allergic disease and that circadian oscillation of cytokine production following IgE-dependent activation is at least in part due to circadian oscillation of FcεRIα.

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-like reaction to cefuroxime: a case report and review of the literature.

We report a case of a 34-year-old woman who received cefuroxime, a second-generation cephalosporin, as treatment for mastitis. She subsequently developed a serum sickness-like reaction (SSLR) with a generalized pruritic rash, joint pains, and fever. She improved upon treatment with systemic steroids. SSLR is well-described to cefaclor, a second-generation cephalosporin. However, there is a paucity of reports of SSLR to other cephalosporins such as this case.

Serum sickness following treatment with rituximab.

Serum sickness, an illness characterized by fever, rash, and arthralgias, can occur in patients who receive chimeric monoclonal antibody therapy. Rituximab, a B cell-depleting chimeric anti-CD20 monoclonal antibody, has been used with increasing frequency in the treatment of rheumatologic illnesses such as rheumatoid arthritis and systemic lupus erythematosus. Serum sickness has only rarely been reported following rituximab therapy. All prior reported cases have been in patients with autoimmune conditions. We describe a case of serum sickness in a patient treated with rituximab for mantle cell lymphoma. We also review the literature of rituximab-induced serum sickness.

Reacción medicamentosa tipo enfermedad del suero / Pharmacological reaction like serum sickness

Presentamos un caso de enfermedad del suero en una paciente de 3 años de edad que, tras realizar tratamiento con amoxicilina-clavulánico durante 7 días, mostró clínica de urticaria y artralgias

We report a case of serum sickness in a 3-year-old patient who presented urticaria and arthralgias after seven days of treatment with amoxicillin-clavulanic

Decay-accelerating factor but not CD59 limits experimental immune-complex glomerulonephritis.

The complex balance between the pro-activating and regulatory influences of the complement system can affect the pathogenesis of immune complex-mediated glomerulonephritis (ICGN). Key complement regulatory proteins include decay accelerating factor (DAF) and CD59, which inhibit C3 activation and C5b-9 generation, respectively. Both are glycosylphosphatidylinositol-linked cell membrane proteins, which are widely distributed in humans and mice. Chronic serum sickness induced by daily immunization with horse spleen apoferritin over 6 weeks was used to induce ICGN in DAF-, CD59- and DAF/CD59-deficient mice, with wild-type littermate mice serving as controls. Both DAF and DAF/CD59-deficient mice had an increased incidence of GN relative to wild-type controls associated with significantly increased glomerular C3 deposition. Disease expression in CD59-deficient mice was no different than wild-type controls. DAF- and DAF/CD59-deficient mice also had increased monocyte chemoattractant protein-1 mRNA expression and glomerular infiltration with CD45(+) leukocytes. Our findings suggest that activation of C3 is strongly associated with experimental ICGN while downstream formation of C5b-9 is of lesser pathogenic importance in this model.

Serum sickness-like reaction to Pamabrom.

Pamabron is a common over-the-counter diuretic used for relief of menstrual-associated symptoms. An urticarial eruption, with systemic complaints consistent with a serum sickness-like reaction, attributed to Pamabron is described. A review of the literature concerning Pamabron and dermatology is discussed.

Cutaneous finding in anti thymocyte globulin induced serum sickness.

Polyclonal anti-thymocyte globulin (ATG) is used as an immunosuppressive agent in the treatment of aplastic anemia (AA). Serum sickness is a recognized side effect of ATG. We observed abnormal skin manifestation in patient with aplastic anemia who had been treated with ATG. We conclude that abnormal immune function caused by aplastic anemia and ATG and corticosteroids may aggravate the signs of serum sickness.

Complement factor h limits immune complex deposition and prevents inflammation and scarring in glomeruli of mice with chronic serum sickness.

Factor H is the major complement regulator in plasma. Abnormalities in factor H have been implicated in membranoproliferative glomerulonephritis in both humans and experimental animals. It has been shown that factor H on rodent platelets functions analogously to human erythrocyte complement receptor 1 in its role to traffic immune complexes to the mononuclear phagocyte system. C57BL/6 factor H-deficient mice (Cfh(-/-)) and wild-type (wt) controls were immunized daily for 5 wk with heterologous apoferritin to study the chronic serum sickness GN model. Immunizations were started in 6- to 8-wk-old mice, which was before the development of spontaneous membranoproliferative glomerulonephritis in some Cfh(-/-) animals. Glomerular deposition of IgG immune complexes in glomeruli was qualitatively and quantitatively increased in Cfh(-/-) mice compared with wt mice. Consistent with the increase in glomerular immune complexes and possibly because of alternative pathway complement activation, Cfh(-/-) mice had increased glomerular C3 deposition. Wt mice developed no glomerular pathology. In contrast, Cfh(-/-) mice developed diffuse proliferative GN with focal crescents and glomerulosclerosis. In addition, there was significantly increased expression of collagen IV, fibronectin, and laminin mRNA in Cfh(-/-) glomeruli. These data show a role for platelet-associated factor H to process immune complexes and limit their accumulation in glomeruli. Once deposited in glomeruli, excessive complement activation can lead to glomerular inflammation and the rapid development of a scarring phenotype.

Immunohistochemical analysis of human serum sickness glomerulonephritis.

AIM: To analyze pathological and immunohistochemical characteristics of glomerulonephritis in human serum sickness. METHODS: Renal biopsy specimens from two female patients with serum sickness that ensued after application of anti-lymphocyte horse globulin for aplastic anemia were analyzed by light microscopy, immunofluorescence, and electron microscopy. To prove the depositions of foreign protein, frozen sections were incubated with fluorescein-conjugated anti-horse protein serum. Immunohistochemical analysis was performed on B5-fixed paraplast-embedded tissue or frozen acetone-fixed sections with the primary antibodies for molecules/cell markers CD35, CD43, CD45RO, CD68, CD2, lysozime, L26, and S100. RESULTS: Diffuse proliferating and necrotizing glomerulonephritis with crescents was found. There were coarse granular mesangial, subepithelial, subendothelial, and intramembranaceous deposits of mainly horse globulin, C3, and IgG. Most mesangium infiltrating cells were macrophages and T-lymphocytes. Electron microscopy revealed hypertrophy of podocytes, but immunohistochemistry did not show their normal CD35 (C3b-receptor) staining. Apart from epithelial cells, main crescent forming cells were macrophages and T-lymphocytes. Rare dendritic cells and abundant infiltration of macrophages, T-lymphocytes, and neutrophiles were found in the interstitium. CONCLUSION: In severe serum sickness, glomeruli and tubuli are destroyed beyond the range usually seen in other types of glomerulonephritis caused by immune complexes, except in cases with widespread crescents. Hypertrophy of podocytes and loss of their normal C3b-receptor staining has not yet been described in the literature. C3b-receptors on podocytes could play a role in pathogenesis of glomerular injury caused by immune complexes.

Serum sickness induced by bupropion.

OBJECTIVE: To describe the first reported case of serum sickness induced by exposure to bupropion. CASE SUMMARY: Bupropion was administered to a 45-year-old white man being treated for depression with psychosis. Within 24 hours after his first dose of bupropion, the patient became delirious and then developed fever, myalgia, arthralgia, and a rash. Bupropion was discontinued after the second dose. With supportive measures, symptoms remitted over two weeks. DISCUSSION: A thorough search for other etiologies of the patient's symptoms was unrevealing, and a clinical diagnosis of serum sickness was made. Given the temporal association between the illness and the introduction of bupropion, this was felt to be the causal agent. No previous reports of serum sickness induced by bupropion were found in the literature. CONCLUSIONS: The previously unreported adverse drug reaction of serum sickness associated with the use of bupropion is demonstrated by this case, based on the temporal relationship and the results of stopping the drug, in light of no other identifiable etiology.