A Rare Case of Severe Skin Reaction to Mycophenolate Mofetil in Systemic Lupus Erythematosus with Lupus Nephritis

Introduction

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease affecting multiple organ systems and skin characterized by unpredictable flares and remissions.¹ Paediatric SLE is associated with significant morbidity and mortality due to severe organ involvement compared to adults, often requiring aggressive immunosuppression.² We report a rare case of a severe maculopapular rash following the initiation of mycophenolate mofetil (MMF) in a 13-year-old female adolescent diagnosed with systemic lupus erythematosus (SLE) and stage IV lupus nephritis. MMF is an effective immunosuppressive agent that selectively inhibits T and B lymphocyte proliferation and is known for its rapid onset of action and relatively mild side effect profile compared to other immunosuppressants.³

While common side effects of MMF include gastrointestinal disturbances and peripheral oedema, severe skin reactions are infrequent. Given the widespread use of MMF, we present a rare case of generalised maculopapular rash induced by the drug.

To date, only two cases of severe skin reactions to MMF have been published in the literature. The first case, reported in 2005, described an acute papulosquamous, psoriatic like skin reaction in a 32-year-old man with generalised seropositive myasthenia gravis.⁴ The second case, reported in 2017 in New York, involved a generalised fixed drug eruption in a 45-year-old women with SLE and lupus nephritis.⁵ This case highlights the adverse reaction to MMF in the context of SLE and lupus nephritis, underscoring the need for close monitoring of patients receiving this treatment. 

Case Presentation

A 13-year-old female was admitted to our hospital with high-grade fever, periorbital puffiness, and abdominal pain. Examination revealed an ulcer on the hard palate. Laboratory findings included proteinuria and hypoalbuminemia. Following a comprehensive workup, including an anti-nuclear antibody ANA profile and the european League Against Rheumatism/American College of Rheumatology EULAR/ACR classification criteria, the patient was diagnosed with systemic lupus erythematosus (SLE) and stage IV lupus nephritis, confirmed by renal biopsy.

The patient was initially treated with intravenous and oral prednisolone, along with hydroxychloroquine. Mycophenolate mofetil (MMF) was introduced two days later. While these medications elicited a favourable clinical response, MMF led to a serious generalized drug reaction. The eruption began with a maculopapular rash and blisters, accompanied by intense itching, facial swelling, and lip oedema. The rash initially appeared on the back and subsequently spread to the face and limbs, eventually covering almost her entire body within 24 hours, with significant pruritus.

The diagnosis of a drug-induced reaction was supported by the resolution of symptoms following the cessation of MMF and the marked improvement with high-dose steroids. Within two days of modifying the treatment, the patient's symptoms completely resolved.

This case highlights the potential for severe cutaneous adverse reactions to MMF in patients with SLE and reinforces the need for vigilant monitoring during immunosuppressive therapy.

Discussion

In paediatric systemic lupus erythematosus (SLE), the clinical course is often more severe and associated with higher mortality rates compared to adult-onset SLE. Renal, neurological, and haematological manifestations such as haemolytic anaemia, thrombocytopenia, and leukopenia are notably more common in children, significantly affecting their long-term health outcomes.⁶ Renal involvement often occurs asymptomatically, underscoring the need for regular monitoring through blood pressure assessments and urinalysis. Typical renal manifestations include proteinuria, haematuria, and renal failure, which can present with symptoms like fatigue, oedema, and nausea.

Lupus nephritis is classified into six categories, with our patient diagnosed with Class IV lupus nephritis (diffuse proliferative lupus nephritis).⁷ The treatment approach for lupus nephritis is tailored based on disease severity. While corticosteroids are a mainstay of treatment, long-term management frequently requires the use of steroid sparing immunosuppressants such as Cyclophosphamide (CYC), Azathioprine (AZA), or Mycophenolate mofetil (MMF).⁸ Mycophenolic acid, the active form of MMF, is considered a more targeted immunosuppressant than CYC. Its selective antiproliferative effects on lymphocytes and mesangial cells in the kidney, along with its ability to inhibit cell adhesion molecules and the migration of inflammatory cells, may offer additional therapeutic advantages in managing lupus nephritis.

Although MMF is generally well-tolerated, with common side effects such as gastrointestinal disturbances,and peripheral oedema, severe skin reactions are rare. This discussion emphasizes the importance of careful observation and individualized patient management to mitigate the risks associated with immunosuppressive treatment in paediatric SLE.^9,10

Given the overall prevalence of MMF use, we present a rare case of generalised maculopapular rash caused by MMF. This case highlights the adverse event caused by MMF in the context of SLE and lupus nephritis, underscoring the need for vigilance in monitoring patients receiving this treatment. Further research is necessary to improve therapeutic strategies and outcomes in this vulnerable population.

Declaration of the patient consent

The authors certify that they have obtained all appropriate consent forms, duly signed by the parent (s)/guardian (s) of the patient. In the form, the parent (s)/guardian (s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal.

The parents understand that the names and initials of their child/children will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflict of Interest

NIL