A Novel Immunomodulatory Strategy to Control Multiple Immune Dysregulation Disorders in a Pediatric Patient

Immune dysregulation can lead to autoimmunity and autoinflammation. The goal of treatment is to balance targeted therapies while avoiding infections or other side effects, which becomes complicated with multiple diagnoses. We present an adolescent female patient with coexisting systemic lupus erythematosus (SLE), Crohn’s disease (CD), psoriasis, and hidradenitis suppurativa (HS) treated with a unique combination of immune suppression. The patient was initially diagnosed with juvenile idiopathic arthritis at four years of age, with subsequent diagnosis of SLE with cerebritis and nephritis at age 14 years. This prompted treatment with plasmapheresis, corticosteroids, and cyclophosphamide, followed by mycophenolate mofetil (MMF). Around the same time, she was hospitalized for a severe, widespread rash, with subsequent diagnoses of psoriasis and hidradenitis suppurativa. She was then initiated on treatment with belimumab for SLE, in combination with MMF and steroids. This resulted in initial improvement of her skin inflammation; however, she then developed severe diffuse dermatitis, hematochezia, and Strep intermedius necrotizing lymphadenitis. The MMF was subsequently discontinued, with ongoing hydroxychloroquine and steroids. Colonoscopy demonstrated pancolitis, consistent with Crohn’s disease. She was started on infliximab, with partial improvement in gastrointestinal (GI) symptoms, but severe ongoing psoriasis. Immune phenotyping was significant for elevated soluble IL2R, IL-17, and IL-6, in addition to T cell lymphopenia with nearly absent B cells post-belimumab. Genetic testing was unrevealing of a monogenic etiology. With ongoing GI and cutaneous symptoms, the patient was started on ustekinumab to target IL-12/IL-23 signaling pathways; however, GI symptoms persisted. She was therefore started on upadacitinib, with the goal of targeting broader T cell and innate inflammation beyond the function of ustekinumab. Antibacterial prophylaxis was also prescribed. On this regimen, all conditions remain well-controlled, without infectious complications. Multidisciplinary collaboration facilitated an individualized treatment strategy incorporating hydroxychloroquine, upadacitinib, and ustekinumab to treat a combination of SLE, HS, psoriasis, and CD, which can lead to Th1/Th17, innate, and type I interferon-mediated inflammation. While each pairwise combination has been described, the simultaneous use of all three medications, post-belimumab, is novel. This underscores the possibility of safely targeting shared and distinct immune pathways between multiple disorders in patients requiring polypharmaceutical immune modulation.