Antibodies antihistone

Antinuclear and antihistone antibodies developed in a 26-year-old man who was taking atorvastatin (22). He had constitutional symptoms and slight headaches but no definite symptoms of lupus. After some months without medication he became seronegative and asymptomatic. 

A18. Amoura, Z., Chabre, H., Koutouzov, S., Lotton, C., Cabrespines, A., et al Nucleosome-restricted antibodies are detected before anti-dsDNA and/or antihistone antibodies in serum of MRL-Mp Ipr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria. Arthritis Rheum. 37, 1684-1688 (1994). 

D6. Deng, J. S., Sontheimer, R. D., Lipscomb, M. F., and Gilliam, J. N., The binding of antihistone antibodies to Crithidia luciliae kinetoplasts is growth cycle-dependent. Arthritis Rheum. 28, 163-168 (1985). 

Antihistone antibodies of the IgA type are significantly correlated with PBC and AIH, occasionally with alcoholic liver diseases. The antihistone antibody is a nuclear antigen. (131) (s. tabs. 5.20 33.1)... 

A 59-year-old man, who had taken amiodarone 200 mg/day for 2 years, developed fever, pleuritic chest pain, dyspnea at rest, a non-productive cough, malaise, and joint pains (211). He had a verrucous endocarditis and a pleuropericardial effusion. He had raised titers of antinuclear antibodies (1 320) with anti-Ro specificity. Serum complement was normal and there were no circulating immune complexes, no cryoglobulins, and no anti-dsDNA, anti-La, anti-Ul ribonucleoprotein, anti-Sm, anti-Scl, 70, anti-Jo 1, antihistone, antiphosphohpid, anticentromere, anticardioli-pin, or anticytoplasmic antibodies. Within 7 days of withdrawal of amiodarone the signs and symptoms started to resolve, and he recovered fuUy with the addition of prednisolone. 

A few observations have suggested that deferiprone can cause a lupus-like syndrome, with antinuclear and antihistone antibodies (33,34), but this suspicion is still unproven (29,35). 

Immunoallergic reactions have been reported with minocycline and include lupus-like syndrome, autoimmune hepatitis, eosinophilic pneumonia, hypersensitivity syndrome, a serum sickness-like illness (29), and Sweet s syndrome (SEDA-21, 262) (SEDA-22, 271). Over 60 minocycline-induced cases of lupus-like syndrome and 24 cases of minocycline-induced autoimmune hepatitis were found in a review of the literature (30). In 13 patients, both disorders co-existed. These patients had symmetrical polyarthralgia/polyarthritis, raised liver enzymes, and positive antinuclear antibodies they were also generally antihistone-negative, and only two patients had p-ANCA antibodies. Minocycline-related lupus can also occur in adolescents (31). 

According to the authors, the patient fulfilled all the criteria for a diagnosis of drug-induced lupus-like syndrome, that is no history of lupus erythematosus before minocycline therapy, the presence of antinuclear antibodies, at least one clinical feature of lupus erythematosus, and prompt recovery after withdrawal of minocycline. She also had positive antihistone antibodies, compatible with drug-induced lupus-like syndrome. 

Seven patients (17-22 years old) developed sjmptoms of arthralgia and arthritis after having taken minocycline 50-100 mg bd for 6-36 months for acne vulgaris (47). Increased titers of perinuclear ANCA were detected in all seven, five had fluorescent antinuclear antibodies, two had antihistone autoantibodies, and one had anticardiohpin antibodies. Symptoms resolved in five patients on withdrawal the other two were treated with corticosteroids and also achieved remissions. 

A 67-year-old white man who had taken phenytoin 300 mg/day for about 15 years developed fever, pericarditis, severe abdominal pain, malaise, and weight loss. He had a positive antinuclear antibody in a titer of 1 80 in a homogeneous pattern, a strongly positive antihistone antibody test, a raised erythrocyte sedimentation rate (115 mm/hour), and a neutrophilia (21 x 10 /1). All these abnormalities resolved within a few weeks of withdrawal. RechaUenge was not performed. 

The mechanisms whereby procainamide causes this lupuslike syndrome are not clear. Procainamide is associated with the production of many antibodies, including antihistone, antiguanosine, anti-DNA, and antiphospholipid antibodies (42). The production of autoantibodies may be due to one of two major mechanisms first, procainamide may act as a hapten, binding to DNA, nuclear protein, or some membrane constituent, the hapten-protein complex stimulating the production of antibodies secondly, it may alter suppressor cell function (43). There is also evidence that procainamide can combine with ribonucleoprotein from damaged myocardium after myocardial infarction, thus precipitating the production of antibodies to ribonucleoprotein (44). 

The antinuclear antibody is positive in virtually all cases and the ESR is often raised. Antihistone antibodies are also present in most cases. The prevalence of serum autoantibodies to high-mobility group (HMG) proteins in the serum of patients with drug-induced lupus-like syndrome varies from protein to protein 67% for HMG-14 and/or HMG-17 compared with 21% for HMG-1 and/or HMG-2. Procainamide-induced lupus is also associated with antibodies to the H2A-H2B dimer (55,56). 

A lupus-like syndrome has occasionally been reported in patients taking quinidine (60,61,64). It usually presents with polyarthralgia, a raised erythrocyte sedimentation rate, and a raised antinuclear antibody titer. It can occasionally be associated with antihistone antibodies and a circulating coagulant. In two cases (65) the syndrome was associated with quinidine and not with procainamide. Lupus anticoagulant has been reported with the use of quinine and quinidine, and an associated antiphospholipid syndrome has been described (66). 

A lupus-like illness (fever, rash, arthritis, renal involvement, and positive antinuclear and antihistone antibodies) developed in three patients 2-8 weeks after they started to take ticlopidine (29). After withdrawal, there was slow but complete resolution in all patients. 

Urinary tract Hydralazine has been associated with ANCA positive pauci-immune glomerulonephritis and pulmonary alveolar hemorrhage [105 ]. In this case anti-double-stranded DNA and antihistone antibodies were present in the absence of full classification criteria for drug-induced lupus-like syndrome. The symptoms and renal function improved after withdrawal of hydralazine and a short course of cyclophosphamide and prednisone. 

Immunologic An elderly woman who received intravenous vancomycin for endophthalmitis developed oral ulcers, fever, and a diffuse er5hhematous body rash after 1 week. Double-stranded DNA and antihistone antibodies suggested a lupus-like syndrome [100 ]. The symptoms improved dramatically after withdrawal of antibiotics and treatment with oral prednisone. 

A girl with nephropathic cystinosis was given cysteamine bitartrate 30 5 mg/kg/day. However, despite adequate intracellular cystine depletion, her renal function declined and she was given enalapril for proteinuria. When she was 14 years old she was found to have a persistently positive lupus anticoagulant with anticardiolipin, antinuclear, and antihistone antibodies, weakly positive double-stranded DNA antibodies, negative extractable nuclear antibodies, an increased ESR, and low serum complement concentrations. Cysteamine was withdrawn and 1 month later the ESR and complement had fallen and the antibody titers had become weakly positive. 

Five to 10% of SLE patients are believed to have drug-induced disease, characterized by the presence of the antihistone antibody. Whereas dermatological, renal, and neuropsychiatric abnormalities are rare, the pleuropulmonary manifestations are particularly common in these cases (297). A similar spectrum of lung manifestations is reported (297,298). 

CRP and D-dimer, positive results for ANA, anti-double stranded DNA and antihistone antibodies and a large left ventricular mass consistent with thrombus in the absence of evidence of a myocardial infarction (imaging) suggested drug-induced systemic lupus erythematosus. Termination of carbimazole resolved the symptoms and laboratory findings. 

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