Occurrence of SARS‐CoV‐2 during mycophenolate mofetil treatment for pemphigus

Editor

We read with great interest the article entitled ‘Should SARS‐CoV‐2 influence immunosuppressive therapy for autoimmune blistering diseases?’ published by Di Altobrando et al. in the JEADV. ¹ This is the first report of COronaVIrus Disease 2019 (COVID‐19) in a patient affected by autoimmune blistering disease (ABD) during immunosuppressive treatment (i.e. azathioprine).

The authors conclude that it is crucial to learn of more cases of ABD patients under immunosuppressive treatment who have developed COVID‐19, in order to better quantify the risk of infection under immunosuppressive therapy.

Also, in our clinical practice, we suspended all follow‐up visits and, in accordance with the directives of the Regional Health Service, we contacted all scheduled patients by phone.

We called a total of 43 patients: 30 affected by bullous pemphigoid, nine by pemphigus and four by mucous membrane pemphigoid. Even though our region is the second most affected by COVID‐19 in Italy (cumulative incidence: 718.72 cases/100 000 inhabitants), ² only one of these patients tested positive for SARS‐CoV‐2, a 65‐year‐old female, affected by pemphigus for 40 months and in therapy with mycophenolate mofetil (MPM) for 38 months.

On March 24, her husband was discovered to be affected by COVID‐19 and was isolated at home, while on March 27, our patient presented severe nausea, fever (37.1°C), anorexia and asthenia; the next day, she tested positive for SARS‐CoV‐2. However, she did not inform us immediately and did not suspend therapy until we contacted her on March 29, when we advised her to interrupt MPM.

We then called her daily for the next days: on April 2, her fever rose to 39°C, but lowered with paracetamol, and continued this pattern over the following 2 days. Starting from April 5, the fever ceased and she progressively improved; on April 8, she referred a total absence of any symptom.

The patient did not experience any pemphigus recurrence, but reported only some posterior tongue ‘discomfort’. Moreover, she never developed cough, dyspnoea, anosmia, ageusia, myalgia or other symptoms of the infection. At present, we are waiting for 2 weeks after the end of symptoms to repeat a swab and restart the immunosuppressive treatment.

Mycophenolate mofetil is an immunosuppressant, antineoplastic and antiviral mediation, used in pemphigus as a corticosteroid‐sparing agent. Due to its antiviral properties, some studies have investigated MPM as a potential therapy for MERS‐CoV. ³ The drug has also been demonstrated to inhibit mRNA expression of pro‐inflammatory cytokines TNF‐α, IL‐6 and IL‐1β, ⁴ which are known to be associated with the progression of COVID‐19 towards the worsening of clinical conditions. ⁵ , ⁶

Even though the in vitro studies showed promising results for MPM against MERS, the in vivo studies suggest that its use is likely to cause more harm than benefit and hence is not likely to be useful against coronavirus infections. ³ However, our patient experienced a very mild form of the disease, without pulmonary complications, suggesting that the immunosuppressant therapy with MPM was not detrimental in the setting of COVID‐19 infection.

Unfortunately, ABDs are rare conditions and it is difficult to collect large cohorts to confirm our observation. This would require much time, which is scarcely compatible with the urgency related to the COVID‐19 sanitary emergency. Therefore, our present knowledge can only be based on anecdotal reports, and it is important to share also the single experience of any centre involved in the management of rare diseases.

Acknowledgement

All authors have agreed to the contents of the manuscript in its submitted form.

The patients in this manuscript have given written informed consent to publication of their case details.