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900 Hyperthyroidism and elevated immune thyroid stimulating globulin (ITSG) following high dose intravenous immunoglobulin therapy
J ALLERGY CLIN IMMUNOL VOLUME 97, NUMBER 1, PART3
897
T h e F o u r Y e a r E x p e r i e n c e w i t h Intravenous Gamma Globulin a t a T e r t i a r y M e d i c a l C e n t e r . R DeGuzman MD. R Rodri~uez MD. E Bernton MD. D Auth PharmD. D Green PharmD. L Smith MD. RJM En,,ler MD. WRAMC, Washington, DC. Reports of the true incidence of adverse reactions to intravenous gamma globulin (IVIG) therapy are limited by the lack of studies documenting reactions in a large number of patients. One study described 6/54 cases of aseptic meningitis (AM) in a series of patients receiving immunomodulatory doses (2gm/kg) of IVIG. (Ann Int Med 1994;121:259) Thirteea cases of acute renal failure (ARF) with immunomodulatory (IM) doses of IVIG have been reported in the literature. We report our experience with IVIG during a 4 year period (19911995) in a tertiary medical center. One hundred eighty-nine patients were treated with IVIG at both replacement (400mg/kg) and IM doses for a variety of conditions. Our results are summarized below:
Abstracts
899
M e t a b o l i c and Hematologic Changes after Different I V I G I n f u s i o n R a t e s . MMS Carnciro Sampaio MD; BT Costa Carvalho MD; D Sol~ MD; RU Sorensen MD; CK Naspitz MD, SAo Paulo, Brazil: New Orleans, LA The concentration of IgG in IVIG preparations has recently been increased by, manufacturers: however, metabolic and hematologic effects of rapid infusion of these new preparations have not been evaluated. We studied metabolic and hematologic changes occurring with increased IgG infusion rates OR) in 7 patients (2-16 years old) with antibody deficiency s3,ndromes who had been treated with 350-600 mg of 3% IgG/kg ever), 3 weeks, for periods ranging from 6 months to 4 years. Initially, IgG concentration of the IVIG preparations was increased to 6, 9 and 12% in consecutive infusions at a constant lgG IR of 4 mg/kg/min. Subsequently, infusion rates were increased to 8, 12 and 16 rag&g/rain using 12% IVIG. Patients were monitored clinically. Blood samples were collected before and 5 and 30 min after infusions to analyze plasma osmolarity, venous blood gases and blood cell counts. Clinieally, all patients tolerated the increase in IVIG concentrations to 12% while the IR was 4 mg/kg/min. However, 1 patient did not tolerate an IR of g mg/kg/min and 2 additional patients developed side effects at an IR of 16 mg/kg/min. There were significant changes in pCO2, HCO3, CO~t and base excess 30 rain after an IR of 16 mg/kg/min. All white cell and platelet counts dropped more than would be expected by the hemodilution effect alone. We conclude that metabolic and hematologic side effects occur with rapid infusion of M G even in patients who tolerate the increased infusion rate clinically.
Benign Eczematous Eruption Following High Dose Intravenous lmmunoglobulin Therapy. RS Pence MD. JS Beard MD. PJM En~ler MD. PM Benson M D . WS Davis MD. VA Carregal DO. WRAMC, Washington., DC. High dose (2-3gm/kg) intravenous irmnunoglobulin (IVIG) is increasingly used as immunomodulator therapy for a wide array of autoimmune diseases including idiopathic thrombocytopenia (ITP) and chionie inflammatory demyelinating polyneuropathy (CIDP). Anecdotal reports of dermatological reactions have included eczema, alopecia, urticaria, erythema multiforme and nonspecific pruritic "rashes". Our experience from 1985-1995 includes 6 cases of eczematous skin eruptions temporally related to the administration of high dose [VIG. Ace Sex Dx IVIG gm (~,m/kR) Rxn Onset Recurred Dose 2 No 59 M CIDP 180 (2) Dose> I Yes 50 M CIDP 240 (3) 55 M CIDP 120 (2) Dose I Yes 14 M ITP 90 (2) Dose 1 N/A 34 M ITP 180 (2) Dose>1 Yes Dose 2 Yes 74 M CIDP 150 (2) All patients noted onset of a pruritic vesicular eruption within 4-7 days aRer infusion of IVIG. Deep seated vesicles gave way to a desquamating, scaling phase which resolved over 10-14 days. The palms, soles, interdigital spaces and frequently extremities and upper chest were involved. Histology of a single punch biopsy was consistent with an acute eczematous reaction. Direct immunofluorescence was negative. Palliative therapy of antihistamines and topical corticosteroids was provided. This self-limiting eruption can be seen on the first dose of IVIG. Recurrence of rash has not prompted discontinuation of therapy. This eruption is reminiscent of other acute vesicular eczematous eruptions: dyshydrutic eczema (palmpholyx), numular dermatitis, and dermatophytid (Id) reactions. Eczematous skin eruptions following IVIG therapy are benign and self-limited. Symptomatic treatment and continued use of IVIG is possible.
Adult Pediatric 'No. of Patients (n=189) 129 60 Male 73 41 Female 56 19 Immunomodulatory 85 28 44 32 Replacement Acute renal failure 2 0 Aseptic meningitis 3 l Acute renal failure occurred in 2/189 (1.1%) patients and aseptic meningitis occurred in 4/189 (2.1%) patients. Consistent with prior reports, we found ARF occurred only with IM doses of IVIG. However, unlike previous reports, 2 of our 4 eases of AM occurred with replacement doses of IVIG. Conclusion: In general, IVIG has a low incidence of severe adverse reactions and aseptic meningitis can occur with replacement doses of IVIG.
898
407
900
Hyperthyroidism And Elevated Immune Thyroid Stimulating Globulin (ITSG) Following High Dose Intravenous Immunoglobulin Therapy. C E B u c k l e y M D , G I Ellis M D , D u r h a m , N C A 32 year old white female presented with continuous antibiotic therapy for frequent infections, normal serum IgG eoncemratious, IgA deficiency (<10 mg/dL), failure to respond to immunization with Pneumovax and to 3 boosts with diphtheria and tetanus texoids, and elevated serum IgE anti-lgA. Intravenous immuaoglohalin therapy was initiated by hospitalization for intravenous desensitization followed by infusion with sufficient IgG to last 3-4 months (1600 mg/Kg). Following the 3rd infusion, the patient developed severe headache, nausea and photophobia without CSF pleocytosis. The headache subsided following treatment with low flow intranasai oxygen and hydration. Three days following discharge the patient developed severe headache, nausea, vomiting, insomnia, a 15 pound weight loss, weakness and severe anxiety leading to hospitalization at home. Clinical and laboratory evaluation revealed evidence of hyperthyroidism. A thyroid scan revealed increased uptake (37%) and the ITSG assay was normal. Anti-thyroid therapy was deferred and the patientwas followed on supportive therapy over a 4 month interval in which the symptoms subsided, the frcc "I"4declined from 4.13 to 1.23 (Normal 0.83-1.90 ng/dL), TSH remained decreased and the ITSG became elevated. The immunoglobulin manufacturer was asked to test retained aliquots of the immunoglobulin lots used to treat the patient for ITSG. High dose intravenous immunoglobtflin therapy can not be excluded as the cause of hyperthyroidism in this patient.
897
T h e F o u r Y e a r E x p e r i e n c e w i t h Intravenous Gamma Globulin a t a T e r t i a r y M e d i c a l C e n t e r . R DeGuzman MD. R Rodri~uez MD. E Bernton MD. D Auth PharmD. D Green PharmD. L Smith MD. RJM En,,ler MD. WRAMC, Washington, DC. Reports of the true incidence of adverse reactions to intravenous gamma globulin (IVIG) therapy are limited by the lack of studies documenting reactions in a large number of patients. One study described 6/54 cases of aseptic meningitis (AM) in a series of patients receiving immunomodulatory doses (2gm/kg) of IVIG. (Ann Int Med 1994;121:259) Thirteea cases of acute renal failure (ARF) with immunomodulatory (IM) doses of IVIG have been reported in the literature. We report our experience with IVIG during a 4 year period (19911995) in a tertiary medical center. One hundred eighty-nine patients were treated with IVIG at both replacement (400mg/kg) and IM doses for a variety of conditions. Our results are summarized below:
Abstracts
899
M e t a b o l i c and Hematologic Changes after Different I V I G I n f u s i o n R a t e s . MMS Carnciro Sampaio MD; BT Costa Carvalho MD; D Sol~ MD; RU Sorensen MD; CK Naspitz MD, SAo Paulo, Brazil: New Orleans, LA The concentration of IgG in IVIG preparations has recently been increased by, manufacturers: however, metabolic and hematologic effects of rapid infusion of these new preparations have not been evaluated. We studied metabolic and hematologic changes occurring with increased IgG infusion rates OR) in 7 patients (2-16 years old) with antibody deficiency s3,ndromes who had been treated with 350-600 mg of 3% IgG/kg ever), 3 weeks, for periods ranging from 6 months to 4 years. Initially, IgG concentration of the IVIG preparations was increased to 6, 9 and 12% in consecutive infusions at a constant lgG IR of 4 mg/kg/min. Subsequently, infusion rates were increased to 8, 12 and 16 rag&g/rain using 12% IVIG. Patients were monitored clinically. Blood samples were collected before and 5 and 30 min after infusions to analyze plasma osmolarity, venous blood gases and blood cell counts. Clinieally, all patients tolerated the increase in IVIG concentrations to 12% while the IR was 4 mg/kg/min. However, 1 patient did not tolerate an IR of g mg/kg/min and 2 additional patients developed side effects at an IR of 16 mg/kg/min. There were significant changes in pCO2, HCO3, CO~t and base excess 30 rain after an IR of 16 mg/kg/min. All white cell and platelet counts dropped more than would be expected by the hemodilution effect alone. We conclude that metabolic and hematologic side effects occur with rapid infusion of M G even in patients who tolerate the increased infusion rate clinically.
Benign Eczematous Eruption Following High Dose Intravenous lmmunoglobulin Therapy. RS Pence MD. JS Beard MD. PJM En~ler MD. PM Benson M D . WS Davis MD. VA Carregal DO. WRAMC, Washington., DC. High dose (2-3gm/kg) intravenous irmnunoglobulin (IVIG) is increasingly used as immunomodulator therapy for a wide array of autoimmune diseases including idiopathic thrombocytopenia (ITP) and chionie inflammatory demyelinating polyneuropathy (CIDP). Anecdotal reports of dermatological reactions have included eczema, alopecia, urticaria, erythema multiforme and nonspecific pruritic "rashes". Our experience from 1985-1995 includes 6 cases of eczematous skin eruptions temporally related to the administration of high dose [VIG. Ace Sex Dx IVIG gm (~,m/kR) Rxn Onset Recurred Dose 2 No 59 M CIDP 180 (2) Dose> I Yes 50 M CIDP 240 (3) 55 M CIDP 120 (2) Dose I Yes 14 M ITP 90 (2) Dose 1 N/A 34 M ITP 180 (2) Dose>1 Yes Dose 2 Yes 74 M CIDP 150 (2) All patients noted onset of a pruritic vesicular eruption within 4-7 days aRer infusion of IVIG. Deep seated vesicles gave way to a desquamating, scaling phase which resolved over 10-14 days. The palms, soles, interdigital spaces and frequently extremities and upper chest were involved. Histology of a single punch biopsy was consistent with an acute eczematous reaction. Direct immunofluorescence was negative. Palliative therapy of antihistamines and topical corticosteroids was provided. This self-limiting eruption can be seen on the first dose of IVIG. Recurrence of rash has not prompted discontinuation of therapy. This eruption is reminiscent of other acute vesicular eczematous eruptions: dyshydrutic eczema (palmpholyx), numular dermatitis, and dermatophytid (Id) reactions. Eczematous skin eruptions following IVIG therapy are benign and self-limited. Symptomatic treatment and continued use of IVIG is possible.
Adult Pediatric 'No. of Patients (n=189) 129 60 Male 73 41 Female 56 19 Immunomodulatory 85 28 44 32 Replacement Acute renal failure 2 0 Aseptic meningitis 3 l Acute renal failure occurred in 2/189 (1.1%) patients and aseptic meningitis occurred in 4/189 (2.1%) patients. Consistent with prior reports, we found ARF occurred only with IM doses of IVIG. However, unlike previous reports, 2 of our 4 eases of AM occurred with replacement doses of IVIG. Conclusion: In general, IVIG has a low incidence of severe adverse reactions and aseptic meningitis can occur with replacement doses of IVIG.
898
407
900
Hyperthyroidism And Elevated Immune Thyroid Stimulating Globulin (ITSG) Following High Dose Intravenous Immunoglobulin Therapy. C E B u c k l e y M D , G I Ellis M D , D u r h a m , N C A 32 year old white female presented with continuous antibiotic therapy for frequent infections, normal serum IgG eoncemratious, IgA deficiency (<10 mg/dL), failure to respond to immunization with Pneumovax and to 3 boosts with diphtheria and tetanus texoids, and elevated serum IgE anti-lgA. Intravenous immuaoglohalin therapy was initiated by hospitalization for intravenous desensitization followed by infusion with sufficient IgG to last 3-4 months (1600 mg/Kg). Following the 3rd infusion, the patient developed severe headache, nausea and photophobia without CSF pleocytosis. The headache subsided following treatment with low flow intranasai oxygen and hydration. Three days following discharge the patient developed severe headache, nausea, vomiting, insomnia, a 15 pound weight loss, weakness and severe anxiety leading to hospitalization at home. Clinical and laboratory evaluation revealed evidence of hyperthyroidism. A thyroid scan revealed increased uptake (37%) and the ITSG assay was normal. Anti-thyroid therapy was deferred and the patientwas followed on supportive therapy over a 4 month interval in which the symptoms subsided, the frcc "I"4declined from 4.13 to 1.23 (Normal 0.83-1.90 ng/dL), TSH remained decreased and the ITSG became elevated. The immunoglobulin manufacturer was asked to test retained aliquots of the immunoglobulin lots used to treat the patient for ITSG. High dose intravenous immunoglobtflin therapy can not be excluded as the cause of hyperthyroidism in this patient.