Antithyroid Drug-Induced Lupus Erythematosus and Immunoglobulin A Deficiency.

BACKGROUND Antithyroid drugs, namely methimazole, are well-known causes of drug-induced lupus erythematosus. This is, however, an infrequent adverse effect. Selective Immunoglobulin A (IgA) deficiency, in contrast, is the most common primary immunodeficiency. Patients with IgA deficiency are at risk of developing infectious diseases, but also autoimmune diseases such as Grave's disease or systemic lupus erythematosus. CASE REPORT We report a case of methimazole-induced lupus erythematosus in a 32-year-old man with renal involvement and concomitant selective IgA deficiency. Symptoms promptly resolved after treatment with hydroxychloroquine and corticosteroids after discontinuation of methimazole. Lupus nephritis required treatment with cyclophosphamide followed by maintenance therapy with mycophenolate mofetil. CONCLUSIONS Drug-induced lupus erythematosus usually develops after a few months or years of exposure to the causative agent. No specific symptoms exist. The diagnosis is not based on particular specific tests, but relies on a set of arguments evoking the role of the medication inducing the condition. The first step in treatment is to stop the causative drug. The therapeutic management of the various manifestations does not differ from that of idiopathic systemic lupus erythematosus. We briefly discuss the relationship between drug-induced lupus erythematosus, Grave's disease, and IgA deficiency, and suggest that IgA deficiency may act as a potential risk factor. Testing for IgA deficiency could be helpful in patients being treated with drugs known to be associated with drug-induced lupus erythematosus.

Immunoglobulin A deficiency following treatment with lamotrigine.

Lamotrigine (LTG) is an anti-epileptic drug and mood-stabilizing agent, whose adverse effects include skin rash and dizziness. Interactions with the immune system are rare, and only a few cases linking hypogammaglobulinemia to LTG treatment have been previously described. In this report, we describe a case in which a patient developed hypogammaglobulinemia, and a subsequent immunoglobulin A (IgA) deficiency, following LTG treatment. As a result of her immunodeficiency, the patient presented with a severe urinary tract infection and required intravenous immunoglobulin. Serum levels of immunoglobulin G and M had recovered by seven months and one month after the discontinuation of LTG, respectively; however, IgA levels remained low (less than 4mg/dL) two years post-treatment. While previous reports have demonstrated IgA deficiencies in patients prescribed other antiepileptic drugs, this is the first case of an IgA deficiency following LTG administration.

Ineffectiveness of folic acid supplementation against phenytoin-induced decrease in salivary immunoglobulin A concentration of epileptic patients.

AIMS: This study was designed to investigate if folate treatment is able to reverse the phenytoin-induced deficiency of salivary immunoglobulin A (IgA). METHODS AND MATERIAL: Twenty-five epileptic patients who had been under phenytoin therapy for at least the last 6 months were randomly selected and subjected to folic acid supplementation, 1 mg/day. The salivary IgA concentration of these patients was measured before and after 2 months of folic acid administration and compared with those of 10 healthy individuals. Independent and paired Student's t tests were used to analyze the effects of phenytoin and folic acid, respectively. RESULTS: Salivary IgA levels of patients receiving phenytoin (11.7 +/- 4.8 IU/l) were significantly (p = 0.039) lower than those of healthy controls (14.8 +/- 3.2 IU/l), but did not statistically (p = 0.541) differ from levels (11.8 +/- 4.6 IU/l) measured after 2 months of folic acid supplementation. CONCLUSIONS: According to these results, folic acid supplementation does not seem to have the efficacy to ameliorate phenytoin-induced salivary IgA hyposecretion.

Acute suppression of serum IgM and IgA in tank workers exposed to benzene.

We investigated associations between benzene exposure and alterations of proteins and cells of the immune system among workers maintaining cargo tanks containing crude oil residues. Individual exposure to benzene, benzene in blood and urine, peripheral blood lymphocytes (total lymphocytes, lymphocytes in subpopulations CD3, CD4, CD8, CD19, CD56 and CD4/CD8 ratio), complement factors C3 and C4 and serum concentration of immunoglobulins (IgG, IgA, IgM and IgE) were analysed among 13 tank workers and nine unexposed referents (catering section). Benzene exposure was measured during three consecutive 12-h work days. Blood and urine samples were collected pre-shift on the first day (baseline), post-shift on the third day, and pre-next shift on the following morning. The time spent in the cargo tank was logged. The individual geometric mean benzene exposure in the breathing zone of tank workers over 3 days was 0.15 p.p.m. (range 0.01-0.62 p.p.m.) (n = 26). The geometric mean benzene concentration in blood post-shift was 12.3 nmol/l among tank workers versus 0.7 nmol/l among the referents. Tank workers showed a decline (versus referents) in IgM from baseline to post-shift (t-test, P = 0.04) and IgA from baseline to pre-next shift (t-test, P = 0.01). They also showed a decline in CD4 T cells from baseline to post-shift (t-test, P = 0.04). Suppression correlated with benzene exposure, benzene concentrations in blood and urine and time spent in the tank. The groups did not differ significantly in the change in other immune parameters. The clinical significance is unknown and warrants further studies.

Carbamazepine induced transient monoclonal gammopathy and immunodeficiency.

Immune abnormalities have been found in many patients receiving anti-epileptic drugs. However, the effects of carbamazepine are still conflicting. We report the case of a 31-year-old woman who began carbamazepine treatment because of idiopathic epilepsy of adulthood. After three years of treatment she developed arthralgias and malaise. Complete immunologic evaluation showed a total absence of immunoglobulin M with decreased levels of immunoglobulin A, positive antinuclear antibodies and monoclonal paraproteinemia type IgG-kappa. The possibility of B cell lymphoma or myeloma was ruled out. Skin testing was negative. Bone marrow examination was normal. After carbamazepine discontinuation, levels of IgA and IgM increased until reaching normal values over 3 years. The monoclonal gammopathy of undetermined significance also disappeared over this period. During this period of immunodeficiency, the patient did not complain of any infectious complications.

Isolated IgA deficiency after chemotherapy for acute myelogenous leukemia in an infant.

IgA deficiency is a relatively common congenital immunodeficiency in children. It can either be asymptomatic or lead to frequent infections, most often of the sinuses and lungs. Intensive chemotherapy for acute leukemia is also profoundly immunosuppressive and can be complicated with life-threatening infections, usually associated with neutropenia and prolonged lymphopenia in the post-bone marrow transplant setting. Isolated, acquired immunoglobulin deficiency that occurs during treatment has been described but is usually transient. In this report, the authors describe a patient with infant acute myelogenous leukemia with acquired, persistent IgA deficiency.

Reversible total IgA deficiency associated with phenytoin treatment.

A 55-y-old male developed long-standing upper respiratory symptoms during phenytoin treatment of epileptic fits. Complete lack of serum IgA was noted repeatedly. Following replacement of phenytoin, normal IgA levels were found and a slow improvement in respiratory symptoms occurred. Immunoglobulin deficiency, in particular low levels of IgA, are not uncommon among phenytoin treated subjects. The occurrence of frequent respiratory infections in such patients justifies the investigation of immunoglobulin levels.

IgA and IgG2 deficiency associated with zonisamide therapy: a case report.

PURPOSE: To report a previously undescribed adverse effect, IgA/IgG subclass deficiency associated with zonisamide (ZNS) therapy. METHODS: Serum IgA and IgG subclass levels were determined by the turbidimetric immunoassay and enzyme-linked immunosorbent assay, respectively, in a 2-year-old boy with postmeningitis sequelae who was treated by ZNS. RESULTS: Four months after initiation of ZNS, combined deficiency of IgA and IgG2 was noted. After cessation of ZNS, serum IgA level was promptly increased. IgG2 level was gradually increased, but remained subnormal after 7 months. CONCLUSIONS: This case documents, for the first time, the action of ZNS on IgG immune system as well as IgA system. If patients with ZNS therapy showed IgA deficiency and recurrent infections, it is preferable to check serum IgG subclass concentrations as well.

Primary Sjögren's syndrome, ulcerative colitis and selective IgA deficiency.

A 24-year-old man with primary Sjögren's syndrome presented with xerophthalmia, xerostomia, and marked parotid swelling. He had a previous history of selective IgA deficiency and ulcerative colitis treated with sulphasalazine. Immunosuppression and withdrawal of sulphasalazine resulted in rapid resolution of the parotitis and disappearance of autoantibodies. A possible role for sulphasalazine in the induction of autoimmunity in this case is discussed.

Cyclosporine A induced colitis and acquired selective IgA deficiency in a patient with juvenile chronic arthritis.

A 12-year-old girl with juvenile chronic arthritis was treated with cyclosporine A for recurrent uveitis. Two years later she presented with weight loss and diarrhea. Investigations suggested drug induced colitis. She improved after withdrawal of cyclosporine and her nonsteroidal antiinflammatory drug. Symptoms recurred on rechallenge with cyclosporine. She has developed a progressive selective IgA deficiency which persists despite cessation of cyclosporine.

Case report: immunoglobulin A deficiency in patients with juvenile rheumatoid arthritis treated with aspirin.

In three patients with juvenile rheumatoid arthritis, serum IgA concentrations were within the normal limit at the onset of disease and before aspirin administration. After aspirin administration, their serum IgA levels gradually decreased. After discontinuation of aspirin, their serum IgA levels gradually increased. These results suggest that IgA deficiency may be due to aspirin administration in such patients. The IgA production in vitro of peripheral blood mononuclear cells from a patient taken 3 months of discontinuation of aspirin was markedly inhibited by preincubation with aspirin. Since the patients' serum IgG and IgM levels hardly changed the heavy chain class switching may be influenced by aspirin through some undefined mechanisms.