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Pemphigus Vulgaris Aggravated: Rifampicin Found at the Scene of the Crime

Cutis. 2022 May;109(5):E19-E21 | doi:10.12788/cutis.0526
May 25, 2022|Cutis
Lifang Hu, MD;Yan Sun, MD;Zhe Gao, MD;Ping Wang, PhD
Author and Disclosure Information

From the Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou City, People’s Republic of China.

The authors report no conflict of interest.

Correspondence: Yan Sun, MD, Department of Dermatology, Hangzhou Third People’s Hospital, 38 West Lake Rd, Hangzhou City, Zhejiang Province, People’s Republic of China, 310000 (sunyan741118@126.com).

Pemphigus vulgaris (PV) is a rare life-threatening condition of the pemphigus group of autoimmune blistering diseases. Systemic glucocorticoids are the cornerstone of management for PV, but complications can arise from their long-term use. We report a case of recurrence of a well-controlled case of PV that could not be alleviated by a combination of steroids, mycophenolate mofetil, and high-dose intravenous immune proteins. The patient had developed numerous complications during previous glucocorticoid therapy, including hypertension, diabetes, glaucoma, cataracts, optic nerve atrophy, aseptic necrosis of the femoral head, osteoporosis, and pulmonary tuberculosis. We determined that recurrence of PV and treatment resistance were consequences of the interaction between the antitubercular agent rifampicin that the patient was taking and corticosteroids. Pemphigus vulgaris was quickly controlled after the rifampicin was discontinued.

Practice Points

  • Long-term use of immunosuppressants requires constant attention for infections, especially latent infections in the body.
  • Clinicians should carefully inquire with patients about concomitant diseases and medications used, and be vigilant about drug interactions.

At 2-month follow-up, no new rash had developed. The patient had already self-discontinued the MMF for 1 month because it was difficult to obtain at local hospitals. The prednisone was reduced to 40 mg daily. Pulmonary computed tomography showed no signs of reactivation of tuberculosis.

Comment

The tuberculostatic compound rifampin induces expression of a number of drug metabolism-related genes associated with cytochromes (especially cytochrome P450 3A4), multidrug resistance (P-glycoprotein and multidrug resistance proteins 1 and 2), uridine 5’-diphospho-glucuronosyltransferase, monoamine oxidases, and glutathione S-transferases.

Drugs that depend on these enzymes for their metabolism are prone to drug interactions when co-administered with rifampicin.4,5 It has been reported that rifampicin reduces the area under the concentration–time curve (AUC) of prednisolone by approximately 30% to 60%; some authors have suggested that, if rifampicin has to be prescribed, a 2- to 3-fold increase in the prednisolone dosage might be indicated.1,4,6,7 Rifampicin also can influence immunosuppressive drugs in organ transplant recipients; for example, an 11-day course of rifampicin 600 mg daily was found to reduce the AUC of oral cyclosporine by approximately 70% and of intravenous cyclosporine by 28%.4,8 Similarly, treatment with rifampicin 600 mg daily for 18 days reduced the AUC of oral tacrolimus by 68% and of intravenous tacrolimus by 35%.4,9

Rifampicin causes a marked reduction in dose-corrected mycophenolic acid exposure when administered simultaneously with MMF through induction of glucuronidation activity and inhibition of enterohepatic recirculation.5,10In in vitro studies, rifampin and other cytochrome P450 inducers have been identified as potentially useful for increasing the rate of cyclophosphamide and ifosfamide (an isomeric analogue of cyclophosphamide) 4-hydroxylation in the human liver in a manner that could have a favorable impact on the clinical pharmacokinetics of these anticancer prodrugs.11 However, clinical analysis of 16 patients indicated that co-administration of ifosfamide with rifampin did not result in changes in the pharmacokinetics of the parent drug or its metabolites.12

The steroids and immunosuppressants mentioned above are widely used in the treatment of autoimmune diseases and drug hypersensitivity in dermatology. Drug interactions should be considered and drug concentrations closely monitored in cases of rifampin co-administration.

Conclusion

In our patient, the use of rifapentine resulted in a recurrence of previously controlled PV and resistance to treatment. The patient’s disease was quickly controlled after discontinuation of rifampicin and with a short-term course of high-dose methylprednisolone and remained stable when the dosages of MMF and prednisone were reduced. This case serves as a reminder for clinicians to consider a drug interaction when treatment fails in order to avoid harming patients, especially those who have an autoimmune disease.

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