Dataset Information

Alopecia and colon ulcers following azathioprine use in a patient with myasthenia gravis: A case report.

ABSTRACT:

Rationale

Azathioprine is a purine analog (PA) used to treat myasthenia gravis (MG). However, some patients are sensitive to azathioprine and develop severe side effects, such as leukopenia, alopecia, and diarrhea soon after using the medication. Pharmacogenetics plays a crucial role in such intolerance.

Patient concerns

A 16-year-old woman with MG developed hair loss, pancytopenia, bloody diarrhea, and fever shortly after azathioprine treatment.

Diagnosis

Pharmacogenetic analysis revealed compound heterozygosity of the nudix hydrolase 15 (NUDT15) gene, which led to suppressed NUDT15 function. Colonoscopy revealed large ulcers with polypoid lesions in the terminal ileum, cecum, ascending colon, and rectum. These are the characteristics of inflammatory bowel disease (IBD).

Interventions

Sanger sequencing of NUDT15 gene and colonoscopy for bloody stool evaluation.

Outcomes

The patient recovered completely from this acute episode after discontinuation of azathioprine treatment. Her hemogram turned back to normal range. There was also no blood in stool during follow-up.

Lessons

Pharmacogenetic effects should be considered when prescribing PA medication. The possibility of secondary or concomitant autoimmune diseases must always be considered in patients with MG.

SUBMITTER: Hsu WY

PROVIDER: S-EPMC9388021 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alopecia and colon ulcers following azathioprine use in a patient with myasthenia gravis: A case report.

Hsu Wan-Yi WY Lin Pei-Chin PC Liu Yi-Ching YC Lin Lung-Chang LC

Medicine 20220801 33

<h4>Rationale</h4>Azathioprine is a purine analog (PA) used to treat myasthenia gravis (MG). However, some patients are sensitive to azathioprine and develop severe side effects, such as leukopenia, alopecia, and diarrhea soon after using the medication. Pharmacogenetics plays a crucial role in such intolerance.<h4>Patient concerns</h4>A 16-year-old woman with MG developed hair loss, pancytopenia, bloody diarrhea, and fever shortly after azathioprine treatment.<h4>Diagnosis</h4>Pharmacogenetic a ...[more]

PMID: 35984164

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Project description:Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, whose clinical hallmark is muscle weakness and early fatigability. Azathioprine (AZA) is commonly used in Myasthenia Gravis therapy. AZA is a purine antagonist, which inhibits the cell cycle in the resting and DNA synthesis phases. It is usually used as an immunosuppressant to block T- and B-cell proliferation. AZA, bioconverted to 6-mercaptopurine by glutathione S-transferase (GST), can be metabolized either through the hypoxanthine phosphoribosyl transferase pathway to active 6-thioguanine nucleotides (6-TGN) or through the thiopurine S-methyltransferase (TPMT) pathway to inactive methyl-thiopurine metabolites. The incorporation of active 6-TGNs into DNA, causing breaks in DNA strands resulting in interference with RNA production and thereby protein synthesis, is responsible for the drug effect. The response to AZA is determined by which metabolic pathway is being favored. While balanced use of both HPRT and TPMT pathways results in responsiveness to AZA, hyperactivity of TPMT skews the balance towards the TPMT pathway and results in unresponsiveness to AZA with no pharmacological effect. In contrast, low TPMT activity skews the balance towards the HPRT pathway, resulting in increasing side-effects due to the accumulation of 6-TGNs. Current treatments for MG therapy are often inadequate because less than 40% of patients achieve complete remission with available drugs. This reflects the lack of drugs acting on target sites for which there is strong evidence of pathogenicity and the inability to identify responder patients. No criteria for responsiveness are available, exposing patients to unpredictable failures and unpredictable side effects. These individuals are at particular risk for adverse drug reaction (ADRs) or therapeutic failure. Genetic profiling with the Affymetrix drug metabolizing enzymes and transports genotyping array offers the ability to determine 1,931 variants and 225 genes involved in drug metabolism and disposition. Accordingly, the study of well-known drug-metabolizing genes can be involved in the specific metabolic pathway of a drug, which is more likely to define genotype-phenotype association and thereby genotype profiles relevant to drug response that can be applied as predictive biomarkers for pharmacological treatment.

Project description:Immune-related neuromuscular disorders are rare and potentially life-threatening adverse events of immune checkpoint inhibitors (ICIs) used in the treatment of cancer. They tend to have a chronic course that usually leads to the permanent discontinuation of immunotherapy. We present a case of pembrolizumab-induced myasthenia gravis that only involved the diaphragm. The patient is a 71-year-old female with a history of stage IV lung adenocarcinoma under maintenance therapy with pemetrexed and pembrolizumab after a complete response to first-line chemo-immunotherapy. She complained of orthopnea since the previous month and was admitted due to hypoxemic respiratory failure. Radiology showed decreased lung volumes and atelectatic areas in both lower lung fields. A subsequent bronchoscopy ruled out infection and cancer recurrence. Pulmonary function tests revealed a mixed disorder with a severe reduction in maximal inspiratory pressure and a large drop in vital capacity in the supine versus the sited position. Ultrasonography of the diaphragm confirmed bilateral diaphragmatic dysfunction, and the patient was initiated on non-invasive ventilation (NIV) during sleep, which led to symptom relief. A neurological physical examination did not reveal any other muscle involvement. Laboratory tests for myasthenic syndromes showed an elevated titer of the anti-acetylcholine receptor antibody, which confirmed the diagnosis of myasthenia gravis. The patient was subsequently treated with corticosteroids, pyridostigmine, and intravenous immunoglobulin and was gradually able to wean off supplemental oxygen. On follow-up, her chest X-ray and spirometry had improved, but she continued sleeping on NIV. Pembrolizumab was stopped, and she is still free of cancer after 9 months. Clinicians treating cancer patients with immunotherapy should be aware of this rare complication and perform timely investigations in any case of orthopnea in the course of ICI therapy to offer specialized management.

Dataset Information

Alopecia and colon ulcers following azathioprine use in a patient with myasthenia gravis: A case report.

Rationale

Patient concerns

Diagnosis

Interventions

Outcomes

Lessons

Publications

Alopecia and colon ulcers following azathioprine use in a patient with myasthenia gravis: A case report.

Similar Datasets

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