Azathioprine hypersensitivity in a patient with peripheral demyelinating polyneuropathy

Hinrichs, R.; Schneider, L.; Ozdemir, C; Staib, G.; Kochanek, K. Scharffetter

doi:10.1046/j.1365-2133.2003.05274.x

Cited by 11 publications

(7 citation statements)

References 8 publications

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“…1 After enzymatic metabolism, the imidazole ring is separated from 6-MP and has been reported to form a protein-bound hapten that may cause hypersensitivity reactions. 2,3 This hypothesis is supported by the fact that patients developing hypersensitivity reactions to AZA may be safely switched to 6-MP. 4 -6 AZA hypersensitivity reactions are rare.…”

Section: Discussionmentioning

confidence: 86%

“…2,16,23,24 In conclusion it can be said that, although rare, hypersensitivity reactions always need to be taken into account in cases where adverse events or aggravation of disease are suspected after the initiation of AZA therapy. Because of their different pathophysiology they have to be clearly separated from toxic effects of the drug, as dose reduction is not an available option.…”

Section: Discussionmentioning

confidence: 97%

“…It was reported to be negative in a patient who had clearly developed an AZA hypersensitivity reaction after re-exposure. 2 Because of gastrointestinal manifestation, especially in the case of chronic inflammatory colitis it is mistaken for active illness. 4,15,16 But it can also mimic aggravation of disease in rheumatoid arthritis, vasculitis, or even neurologic illnesses such as myasthenia gravis.…”

Section: Discussionmentioning

confidence: 99%

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Azathioprine-Associated Hypersensitivity Reaction in a Patient With Churg Strauss Vasculitis

Lehmann¹,

Schöelmerich²,

Haerle³

2010

JCR: Journal of Clinical Rheumatology

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A zathioprine (AZA) has been used since the beginnings of immunosuppressive therapy in organ transplantation, and later, to treat various autoimmune diseases. We report a case of a patient with an AZA-induced hypersensitivity reaction, a rare but potentially harmful side effect. CASEA 59-year-old male patient presented with elevated systemic inflammatory markers, blood eosinophilia of 53%, clinical and laboratory signs of myositis, bilateral pulmonary infiltrates, and peripheral polyneuropathy with rapid onset and progression. He had been suffering from asthma and chronic rhinitis for years. Antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, and antisynthetase-antibodies were negative, and complement levels were found to be within the normal range. Sarcoidosis, hematologic disorders, malignant, and allergic causes were excluded. A clinical diagnosis of a Churg Strauss vasculitis was made. After prednisone pulse and intravenous cyclophosphamide therapy, the patient improved rapidly, eosinophils returned within the normal range, pulmonary infiltrates vanished, and the polyneuropathy remained stable. After remission induction, a maintenance therapy with AZA was initiated with the patient, and the dose tapered to 200 mg/d. Initially, the drug was well tolerated. However, after 2 weeks of AZA treatment, the patient was presented to our emergency department with an acute onset of fever of up to 39°C, nausea, vomiting, and diarrhea. Laboratory tests showed an elevated C-reactive protein concentration of 74 mg/L, and a normal white blood count with relative neutrophilia of 92% and lymphopenia of 1.5%. Level of eosinophils was not elevated (0.7%). Liver function tests were normal. Urine analysis, chest x-ray, and abdominal ultrasound revealed no bacterial focus. AZA was stopped, and the patient was discharged with antibiotic treatment, as he refused to be admitted to the hospital. The patient recovered completely within a couple of days, and blood tests showed inflammatory markers and differential blood count within the normal range; therefore, AZA treatment was resumed about 3 weeks later. After 1 dose of AZA (50 mg), he developed the same symptoms and laboratory changes as those seen before. AZA hypersensitivity was now suspected, and the medication was stopped. Without any antibiotic treatment, the patient again recovered within days. C-reactive protein and differential blood count returned within the normal range. Immunosuppressive therapy was then switched to methotrexate without any sign of relapse of the apparent Churg Strauss vasculitis.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Azathioprine-Associated Hypersensitivity Reaction in a Patient With Churg Strauss Vasculitis

Lehmann¹,

Schöelmerich²,

Haerle³

2010

JCR: Journal of Clinical Rheumatology

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“…Azathioprine is contraindicated in patients with known hypersensitivity to the drug 27–29 (Grade A; level III). Evidence of teratogenicity with azathioprine in humans is equivocal, 30 but adequate contraceptive precautions are advised when either partner is taking azathioprine.…”

Section: Azathioprine Contraindicationsmentioning

confidence: 99%

“…Azathioprine is contraindicated in patients with known hypersensitivity to the drug [27][28][29] (Grade A; level III). This may be metabolized in three ways: (i) methylation to inactive 6-methyl mercaptopurine (6-MMP) catalysed by thiopurine methyl transferase (TPMT); (ii) oxidation to inactive 6-thiouric acid catalysed by xanthine oxidase (XO); and (iii) hypoxanthine guanine phosphoribosyl transferase (HPRT) catalyses the conversion of 6-MP to 6-thioinosine 5-monophosphate which is further converted to 6-thioguanine.…”

Section: Azathioprine Contraindicationsmentioning

confidence: 99%

Guidelines for prescribing azathioprine in dermatology

2004

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Azathioprine has been available as an immunosuppressive agent for over 40 years, and current routine usage in dermatology is not restricted to licensed indications. Advances in understanding the metabolic fate of azathioprine have led to significant changes in prescribing practice and toxicity monitoring by U.K. dermatologists. The current state of knowledge concerning the use of azathioprine in dermatology is summarized, with identification of strength of evidence. Clinical indications and contraindications for azathioprine usage in dermatology are identified. Evidence-based recommendations are made for routine safety monitoring of patients treated with azathioprine, including pretreatment assessment of red blood cell thiopurine methyltransferase activity.

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Sudden Conjunctivitis, Lymphopenia, and Rash Combined With Hemodynamic Changes (SCoRCH) After Trimethoprim-Sulfamethoxazole Use

et al. 2023

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ImportanceTrimethoprim-sulfamethoxazole (TMP-SMX) hypersensitivity reaction, ranging from circulatory shock to aseptic meningitis and respiratory failure, is a potentially life-threatening condition with dermatologic relevance.ObjectiveTo describe the mucocutaneous findings and clinical features of TMP-SMX hypersensitivity reaction.Design, Setting, and ParticipantsThis was a retrospective case series study of 7 patients who developed a characteristic rash, hemodynamic changes, and end-organ dysfunction after treatment with TMP-SMX at a large university hospital system during January 2013 to March 2022.ExposuresTreatment with TMP-SMX within 2 weeks of the reaction.Main Outcome and MeasuresDescriptions of the condition, including the demographic information of the affected population, the reaction timeline, and mucocutaneous and clinical features.ResultsThe cohort comprised 7 patients (median [range] age, 20 [15-66] years; 4 female and 3 male). The most common mucocutaneous findings were generalized sunburn-like erythema without scale, conjunctivitis, and mild facial and acral edema. Three patients had previous exposure to TMP-SMX and developed symptoms in 1 day or less, while those without prior exposure presented from 4 to 11 days after drug initiation. Among the 7 patients, 6 had fever, 7 had hypotension, and 7 had tachycardia. All patients had lymphopenia and evidence of end-organ dysfunction with either kidney or liver involvement. Median (range) time to resolution was 72 (48-96) hours.Conclusions and RelevanceThis retrospective case series indicates that SCoRCH (sudden conjunctivitis, lymphopenia, and rash combined with hemodynamic changes) should be considered in the differential diagnosis of patients presenting with acute generalized sunburn-like erythema, conjunctivitis, systemic symptoms, and hemodynamic changes in the setting of recent TMP-SMX use.

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Azathioprine hypersensitivity in a patient with peripheral demyelinating polyneuropathy

Cited by 11 publications

References 8 publications

Azathioprine-Associated Hypersensitivity Reaction in a Patient With Churg Strauss Vasculitis

Azathioprine-Associated Hypersensitivity Reaction in a Patient With Churg Strauss Vasculitis

Guidelines for prescribing azathioprine in dermatology

Sudden Conjunctivitis, Lymphopenia, and Rash Combined With Hemodynamic Changes (SCoRCH) After Trimethoprim-Sulfamethoxazole Use

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