unexplained weight loss, diagnosis pSA and AK, on Simponi Aria, low dose

Differential diagnosis for unexplained weight loss in a patient with psoriasis and ankylosing spondylitis on Simponi Aria (golimumab) and low-dose methotrexate includes:

• Disease activity or flare of underlying inflammatory spondyloarthritis or psoriatic arthritis: Active inflammation can cause systemic symptoms like weight loss and fatigue. Axial and peripheral disease progression should be considered especially if the current therapy is insufficient or there is emerging axial involvement (inflammatory back pain) NICE CKS,NICE NG65,Grinnell-Merrick et al. 2020.
• Adverse effects or toxicity from immunosuppressive therapy: Methotrexate and biologic DMARDs, such as TNF inhibitors, can cause side effects including gastrointestinal intolerance, hepatic toxicity, or infections that may lead to weight loss NICE CKS,NICE NG65.
• Infection: Immunosuppression increases risk for opportunistic infections (e.g., tuberculosis, fungal, viral), which can cause systemic symptoms and weight loss. A focused infectious screen and vigilance for signs of infection is essential given the use of Simponi Aria and methotrexate NICE CKS,NICE NG65.
• Malignancy: Patients on long-term immunosuppression, notably with methotrexate and TNF inhibitors, have a slightly increased risk of lymphoma or skin cancers, that may present with unexplained weight loss NICE CKS,NICE NG65.
• Concurrent inflammatory or comorbid conditions: Extra-articular manifestations associated with spondyloarthritis, such as inflammatory bowel disease (IBD), could be present or worsening, contributing to weight loss. Screening for symptoms/signs of IBD or other systemic disease is prudent NICE CKS,Wine et al. 2025.
• Mechanical versus inflammatory back pain or new axial involvement: New onset or worsening of axial symptoms suggesting inflammatory back pain may indicate insufficient disease control, impacting systemic features Grinnell-Merrick et al. 2020.

Appropriate management approach:

• Clinical and laboratory re-assessment: Confirm or exclude active spondyloarthritis or psoriatic arthritis activity via history, examination focusing on inflammatory back pain features, enthesitis, dactylitis and skin disease, plus inflammatory markers (CRP, ESR) NICE CKS,NICE NG65,Grinnell-Merrick et al. 2020.
• Review of immunosuppressive therapy: Evaluate adherence, dosage adequacy, and potential drug toxicity, including liver function tests. Consider drug level monitoring or antibody testing if available to assess biologic efficacy NICE CKS,NICE NG65.
• Screen for infection: Perform appropriate infection screening (e.g., TB, chest X-ray, blood cultures if indicated), especially due to combined biologic and methotrexate therapy NICE CKS,NICE NG65.
• Exclude malignancy: Based on clinical suspicion, consider investigations for lymphoma or other cancers, including imaging and appropriate referrals NICE CKS,NICE NG65.
• Investigate for IBD or other systemic conditions: If gastrointestinal symptoms or other clues exist, consider stool studies, faecal calprotectin, imaging or endoscopy to evaluate for IBD Wine et al. 2025.
• Rheumatology referral: Given the complexity and need to optimise treatment, specialist input is recommended. Treatment escalation may include switching or adding biologics (e.g., IL-17 inhibitors) if disease remains active NICE CKS,NICE NG65,Grinnell-Merrick et al. 2020.
• Non-pharmacological interventions: Support with physiotherapy, exercise programmes and patient education to improve overall function NICE CKS,NICE NG65.

Summary: Unexplained weight loss in this patient population may be multifactorial with possible disease flare, infection, malignancy, or treatment adverse effects. A systematic evaluation including clinical, laboratory, and imaging assessment is mandatory. Optimisation of immunosuppressive therapy with specialist rheumatology collaboration is key, alongside exclusion/treatment of alternative causes NICE CKS,NICE NG65,Grinnell-Merrick et al. 2020,Wine et al. 2025.