Asian Journal of Medicine and Health

Ursodiol as Salvage Therapy in Steroid- and MMF-Refractory Cholestatic Immune Checkpoint Inhibitor Hepatitis with Concurrent Pneumonitis

Thu, 15 Oct 2026 00:00:00 +0000

Introduction: Immune checkpoint inhibitor hepatitis (ICIH) occurs in 0-30% of patients receiving PD-L1 and CTLA-4 inhibitors, while checkpoint inhibitor pneumonitis (CIP) affects 2-19% of patients. ICIH typically presents as steroid-responsive hepatocellular injury. Cholestatic and mixed patterns are rare and are more frequently steroid-refractory, requiring second-line immunosuppression. Concurrent ICIH and checkpoint inhibitor pneumonitis in a single patient is exceptionally rare. The combination of ICIs with other immunosuppressants may magnify hepatotoxicity and pneumonitis through overlapping immune dysregulation. Ursodiol shows promise for cholestatic drug-induced liver injury because of its choleretic, hepatoprotective, and immunomodulatory mechanisms, but it remains poorly studied in ICIH. We present a case of steroid-refractory cholestatic ICIH with concurrent recurrent pneumonitis that was associated with a marked biochemical response to ursodiol.

Case Presentation: A 63-year-old male with metastatic non-small cell lung carcinoma (NSCLC), initially diagnosed in 2017, developed recurrence in 2023. He received eight cycles of carboplatin/paclitaxel followed by pembrolizumab/osimertinib combination therapy. He presented with dyspnoea and was found to have a subsegmental pulmonary embolism, with diffuse bilateral ground-glass opacities on CT. Bronchoalveolar lavage (BAL) confirmed CIP. Simultaneously, cholestatic transaminitis developed (AST 166 U/L, ALT 168 U/L, ALP 336 U/L). The autoimmune workup was negative, and viral testing showed resolved hepatitis B. Despite high-dose corticosteroids for pneumonitis, liver enzymes progressively worsened over seven days, peaking at AST 388 U/L, ALT 410 U/L, ALP 337 U/L, and total bilirubin 3.4 mg/dL. Liver biopsy showed hepatitis and moderate portal inflammation consistent with ICIH. Pembrolizumab was permanently discontinued, but osimertinib was continued with high-dose corticosteroids. Because of steroid-refractory disease, mycophenolate mofetil (MMF) 500 mg twice daily was added, with an initial partial response. However, the patient developed rebound transaminitis (ALP 405 U/L, AST 227 U/L). He had recurrent episodes of severe pneumonitis that required escalating corticosteroid doses; therefore, MMF and osimertinib were held because of worsening infection risk and recurrent pneumonitis. Ursodiol 500 mg daily was initiated as adjunctive therapy for the cholestatic pattern. Liver function tests showed marked improvement on ursodiol monotherapy. Liver function tests had nearly normalised within three weeks of therapy: AST 19 U/L (95% reduction from peak), ALT 24 U/L (94% reduction), and ALP 147 U/L (56% reduction).

Discussion: This case highlights synergistic drug toxicities and therapeutic challenges in managing overlapping immune-related adverse events. The concurrent use of pembrolizumab and osimertinib may amplify both hepatotoxicity and pneumonitis compared with monotherapy, requiring enhanced surveillance. Only 10-15% of ICIH cases fail corticosteroid therapy, and cholestatic-pattern ICIH is generally more treatment-refractory than hepatocellular patterns. Managing concurrent refractory hepatitis and pneumonitis limits conventional treatment options. Ursodiol has been proposed to have choleretic effects, hepatocyte membrane-stabilising activity, anti-apoptotic properties, and immunomodulatory effects through decreased MHC class I expression. Increased MHC class I expression has been reported in cholestatic-pattern injury. The patient's detailed longitudinal clinical course, including laboratory trends and therapeutic modifications, is provided in Supplementary Appendix 1.

Conclusions: This case illustrates the potential risk of severe, overlapping immune-related adverse events with combination ICI-TKI therapy and the particular challenge of cholestatic-pattern ICIH. Most notably, ursodiol was associated with substantial biochemical improvement as salvage therapy in steroid- and MMF-refractory disease, suggesting that it may warrant consideration early in cholestatic ICIH, particularly when infection risk precludes conventional immunosuppression. This case adds to the limited literature supporting the role of ursodiol and highlights the need for prospective trials. Clinicians should remain aware of the synergistic toxicities of immunotherapy and consider alternative therapeutic approaches for refractory cases.

Relapsing–Remitting Multiple Sclerosis in a Nigerian Woman: Diagnostic and Therapeutic Challenges in a Low-Resource Setting

Tue, 13 Oct 2026 00:00:00 +0000

Background: Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disorder of the central nervous system that is increasingly recognised in sub-Saharan Africa. Diagnostic and treatment delays remain common because of a low index of suspicion, limited access to neuroimaging, overlap with infectious and degenerative neurological disorders, and limited availability of medication.

Case Presentation: We report the case of a 43-year-old Nigerian woman who presented with a three-year history of recurrent lower limb paraesthesia and stiffness, followed by the subacute onset of visual blurring and right facial paraesthesia. Neurological examination was largely unremarkable. Magnetic resonance imaging (MRI) of the brain demonstrated multiple periventricular, deep white matter, pontine, and cerebellar peduncular T2/FLAIR hyperintense lesions with characteristic Dawson’s fingers. Cerebrospinal fluid analysis revealed positive oligoclonal bands (type 2). Whole-spine MRI showed extensive multilevel degenerative disc disease with spinal canal stenosis, as well as features consistent with demyelinating pathology. A diagnosis of relapsing–remitting multiple sclerosis was made based on the 2017 McDonald criteria. The patient showed significant clinical improvement following corticosteroid therapy. Although interferon beta-1a (Avonex) was advised as disease-modifying therapy, access was limited because of its unavailability.

Conclusion: This case highlights the diagnostic complexity of multiple sclerosis in low-resource settings, particularly when extensive degenerative spine disease coexists. Increased awareness and early utilisation of MRI and CSF analysis are important for prompt diagnosis of MS, while limited treatment resources may affect outcomes in Nigeria.

Evidence for Harm Reduction Programming: Prevalence and Risk Factors of Tramadol Use among Adolescents in Juba, South Sudan

Mon, 12 Oct 2026 00:00:00 +0000

Background: Tramadol misuse among adolescents is an emerging public health concern in several African settings, facilitated by its accessibility and non-medical use. In Juba, South Sudan, empirical evidence on the prevalence and factors associated with tramadol use among adolescents remains limited.

Aim: This study assessed the prevalence and risk factors of tramadol use among adolescents in Juba, South Sudan.

Methods: A cross-sectional survey was conducted among 297 adolescents aged 12–17 years in Juba. A structured questionnaire gathered data on socio-demographic characteristics and tramadol use, which the researchers then entered using EpiData and analysed with SPSS version 27. Descriptive and inferential statistics, including chi-squared tests and Cramer's V, were computed with 95% confidence intervals (CIs). The study adhered to ethical standards.

Results: The sample was predominantly male (82.8%; 95% CI: 78.5–86.9) and aged 15–17 years (80.8%; 95% CI: 76.1–85.2). Most lived in low-income households (56.9%; 95% CI: 51.2–62.3), and 57.9% (95% CI: 51.9–63.6) engaged in paid work. The lifetime prevalence of tramadol use was 81.1% (95% CI: 76.8–85.9), past-12-month use was 72.1% (95% CI: 66.7–77.4), and past-30-day use was 62.6% (95% CI: 56.9–68.4). Initiation commonly occurred at ages 12–14 years (37.7%) and 15–17 years (43.1%). Regular use was notable, with 19.2% using tramadol several times per week and 13.5% using it daily or almost daily. Tramadol use was significantly associated with age (χ² = 39.73, p < .001, Cramer's V = 0.366), residential location (χ² = 60.91, p < .001, V = 0.453), household size (χ² = 22.78, p < .001), employment status (χ² = 29.31, p < .001), perceived family economic status (χ² = 12.22, p = 0.002), peer introduction (χ² = 120.67, p < .001, V = 0.637), peer pressure (68.5% vs. 57.1%; p = 0.043), and situational motives such as coping with stress (χ² = 125.91, p < .001, V = 0.651), among others.

Conclusion: Tramadol use is highly prevalent among adolescents in Juba, begins in early adolescence, and frequently occurs at regular or daily intervals. Use is shaped by an interplay of demographic, socioeconomic, peer, and psychosocial factors, with peer-related influences and situational motives showing the strongest associations. The findings indicate an urgent need for school-based prevention, regulation of tramadol access, and family-level interventions targeting young people in Juba as part of harm-reduction programming.