Incidence of serum sickness following Indian polyvalent antivenom therapy in a cohort of snake-envenomed patients in rural Sri Lanka.

INTRODUCTION: Serum sickness is a poorly reported delayed adverse reaction following snake antivenom therapy. We aimed to assess the frequency of serum sickness associated with administering Indian polyvalent antivenom in Sri Lanka. METHODS: We recruited patients from the Anuradhapura snakebite cohort who were admitted to a rural tertiary care hospital in Sri Lanka over one year period. Patients were interviewed over the phone 21 to 28 days post-envenoming to collect data on clinical effects: fever/chills, arthralgia/myalgia, rash, malaise, headache, abdominal pain, and nausea/vomiting. The presence of three or more symptoms between the 5th to 20th days after snake envenoming was defined as serum sickness. RESULTS: We were able to contact 98/122 (80%) patients who received antivenom and 423/588 (72%) who did not receive antivenom during the study period. The treated patients received a median dose of 20 vials (interquartile range: 20-30) of Indian polyvalent antivenom and of them, 92 (92%) received premedication. However, 67/98 (68%) developed acute adverse reactions to antivenom, including 19/98 (19%) developing anaphylaxis. Only 4/98 (4%) who received antivenom met the criteria for serum sickness, compared to none who did not receive antivenom therapy. All patients who developed serum sickness were envenomed by Russell's vipers, were premedicated, and received VINS Bioproducts antivenom. Three of them were treated with hydrocortisone in the acute stage, as premedication or as a treatment for acute adverse reactions of antivenom. Although all four patients sought medical advice for their symptoms, only one was clinically suspected to be serum sickness and treated, while the others were treated for infections. CONCLUSIONS: We confirmed that Indian polyvalent antivenom use in Sri Lanka is associated with high rates of acute adverse reactions. In contrast to studies of other antivenoms only a small proportion of patients developed serum sickness.

Ofatumumab for multirelapsing membranous nephropathy complicated by rituximab-induced serum-sickness.

Rituximab (375 mg/m2) achieved remission of the first episode and six relapses of nephrotic syndrome (NS) in a young male patient with podocyte phospholipase A2 receptor (PLA2R)-related membranous nephropathy (MN) refractory to steroids and cyclosporine. Between-treatments interval averaged 17.4±4.2 months. The seventh infusion was complicated by delayed serum-sickness, which resolved with steroids. On subsequent relapse, the fully human anti-CD20 monoclonal antibody ofatumumab (300 mg) achieved remission of the NS, without significant side effects. Circulating CD19+ B cells were depleted, proteinuria decreased from 10.9 to 1.3 g/day, and serum albumin, immunoglobulin levels and glomerular filtration rate normalised. Twenty-eight months later, despite transient anti-PLA2R depletion, ofatumumab (100 mg) failed to induce remission of the eighth relapse. Remission was safely achieved 5 months later with repeated ofatumumab infusion (300 mg). This treatment (€723) was less expensive than rituximab (€1801). Ofatumumab could be a safe and cost/effective rescue therapy for patients with MN sensitised against rituximab.

Presumed serum sickness following thymoglobulin treatment of acute cellular rejection of a cardiac allograft.

Serum sickness is a hypersensitivity reaction to proteins in antiserum derived from nonhuman animal sources and can be seen in patients being treated with antiserum to prevent transplant rejection. Serum sickness may display variable clinical presentations. Because cutaneous findings may be the initial symptom in some cases, it is important for dermatologists to be able to recognize this condition given its potentially life-threatening symptoms. We present a case of a 35-year-old man with presumed serum sickness after receiving thymoglobulin for the treatment of acute cellular rejection of a heart transplant. The clinical presentation, laboratory findings, and treatment options are reviewed.

Enfermedad del suero-like inducida por bupropión / Serum-like disease inducted by bupropion

No disponible

CD11b is protective in complement-mediated immune complex glomerulonephritis.

In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex-mediated glomerulonephritis in CfH(-/-) mice chimeric for wild-type, CfH(-/-), CD11b(-/-), or FcRγ(-/-) bone marrow stem cells. Glomerulonephritis was worse in CD11b(-/-) chimeras compared with all others, whereas disease in FcRγ(-/-) and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b(-/-) chimeras had significantly more M1 macrophages and CD4(+) T cells. The renal dendritic cell populations originating from bone marrow-derived CD11c(+) cells were similar in all experimental groups. CD11b(+) cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b(-/-) chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex-mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4(+) T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney.

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.

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

Serum sickness and uveitis.

Serum sickness is immune response to a foreign antigen, usually a heterologous protein. Incidence rate is less than 0.5%. Antigens and responding antibodies form circulating immunocomplex that is characteristic for serum sickness. The condition occurs 7-15 days after exposure to the antigen, usually with clinical picture of glomerulonephritis. The immunocomplex circulates to other tissues where it sediments and causes inflammation, such as arteritis, neuritis, synovitis. The aim of this research is to present the break out of serum sickness in form of anterior uveitis due to azithromycin therapy administered by mouth. Identifying of anterior uveitis may help in early diagnostics and treatment 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.

Extrahepatic manifestations of chronic hepatitis B.

Several extrahepatic manifestations are associated with chronic HBV infection, many with significant morbidity and mortality. The cause of these extrahepatic manifestations is generally believed to be immune mediated. PAN is a rare, but serious, systemic complication of chronic HBV affecting the small- and medium-sized vessels. PAN is seen more frequently in North American and European patients and rarely in Asian patients. PAN ultimately involves multiple organ systems, some with devastating consequences, though the hepatic manifestations are often more mild. The optimal treatment of HBV-associated PAN is thought to include a combination of antiviral and immunosuppressive therapies. HBV-associated GN occurs mainly in children, predominantly males, in HBV endemic areas of the world, but is only occasionally reported in the United States. In children, GN is usually self-limited with only rare progression to renal failure. In adults, the natural disease course of GN may be more relentless, slowly progressing to renal failure. Immunosuppressive therapy in HBV-related GN is not recommended, but antiviral therapy with alpha-interferon has shown promise. The serum-sickness like "arthritis-dermatitis" prodrome is seen in approximately one third of patients acquiring HBV. The joint and skin manifestations are varied, but the syndrome spontaneously resolves at the onset of clinical hepatitis with few significant sequelae. Occasionally, arthritis following the acute prodromal infection may persist; however, joint destruction is rare. The association between HBV and mixed essential cryoglobulinemia remains controversial; but a triad of purpura, arthralgias, and weakness, which can progress to nephritis, pulmonary disease, and generalized vasculitis, has characterized the syndrome. Finally, skin manifestations of HBV infection typically present as palpable purpura. Though papular acrodermatitis of childhood has been reported to be caused by chronic HBV, this association remains controversial.

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.

[Drug-induced urticaria]. / Urticaires médicamenteuses.

According to different estimations, the systemic or topical administration of drugs is the 2nd or 3rd identified cause of urticarias. Urticaria may be the leading symptom of drug-induced immuno-allergic reactions such as anaphylaxis or serum sickness. More often, it is the manifestation of non-immune reactions by drug-induced direct release of histamine, activation of complement or enzymatic impairment of the metabolism of arachidonic acid derivatives. Skin tests may be helpful for the demonstration of the responsibility of drugs in the immuno-allergic reactions. Whatever the mechanism may be, one should dissuade from provocation reintroduction of the suspected drug without an extreme wariness.

Contrast-enhanced magnetic resonance imaging in a nontraumatic rabbit osteonecrosis model.

We investigated early osteonecrosis using in vivo magnetic resonance imaging in a nontraumatic rabbit model of serum-sickness osteonecrosis in which osteonecrosis was induced after two intravenous injections of horse serum with a 3-week interval. One week (group A, 17 rabbits) and 3 weeks (group B, 13 rabbits) after the second serum injection, coronal magnetic resonance images of the femur were obtained and it was removed for histological study. Some of the necrotic lesions in the diaphysis were detected on T1-weighted, T2-weighted, or fat-suppression T1-weighted images (six of 24 necrotic lesions in group A and 16 of 18 in group B), and all of the necrotic lesions in the epiphysis, metaphysis, and diaphysis were detected on T1-weighted or fat-suppression T1-weighted images enhanced with gadolinium-diethylene triamine pentaacetic acid. All focal homogeneous enhanced areas on T1-weighted or fat suppression T1-weighted images corresponded to necrotic lesions (22 of 24 necrotic lesions in group A and 18 of 18 in group B); the contours of the enhanced areas were displayed more clearly on the fat-suppression T1-weighted than on the T1-weighted images. The fat-suppression T1-weighted image enhanced with gadolinium-diethylene triamine pentaacetic acid was thus the most sensitive and specific of five kinds of magnetic resonance images for the detection of early necrotic lesions. The results suggest that this image may be useful for early diagnosis of clinical osteonecrosis and for obtaining information about the pathomechanism of osteonecrosis.

[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.

Participation of endothelial cells in the development of glomerulosclerosis: a study on murine serum sickness nephritis with mitomycin C.

To investigate the participation of endothelial cells in glomerulosclerosis, the study was performed in serum sickness nephritis (SSN) with administration of mitomycin C (MMC). SSN was induced in 8 week male Fisher rats by sensitizing them with albumin, chicken egg (EA). Then MMC (0.5 mg/kg bodyweight) was injected daily for 3 days and they were killed at 1, 2, 4 and 6 week intervals. Significant mesangial expansion and sclerosis were observed in the experimental mixed SSN-MMC group in comparison to the SSN or MMC control group from 1 week to 6 weeks (P < 0.05). Moreover at 1 week, double contour appearance of the glomerular capillary wall, basement membrane splitting and disruption were observed light microscopically in the mixed SSN-MMC group. Electron microscopy revealed peripheral capillary basement membrane disruption with huge subepithelial, mesangial osmiophilic deposits and epithelial foot process effacement. At 6 weeks, disappearance of the endothelial cell fenestration and subepithelial basement membrane-like material formation were observed in the MMC group. Based on these results, it is suggested that MMC induced assault on the glomerular endothelial cell produces prominent glomerular capillary basement membrane disruption at the early phase of SSN, resulting in the accumulation of huge subepithelial and mesangial deposits, mesangial cell proliferation, production of the extracelluar matrix component and initiation of glomerulosclerosis.