Case Presentation: 26 yo M with X-linked agammaglobulinemia admitted for RLE extremity non healing wound and abdominal distention found to have hepatosplenomegaly (liver 23 cm), moderate to large ascites, transaminitis (ALP 300, AST/ALT 43/12), hyperbilirubinemia (T bili 6.5->7.5), coagulopathy (INR 1.75 with pancytopenia. On ultrasound porto-systemic collaterals and splanchnic vessels were reported patent. MRI abdomen showed questionable cirrhosis with portal hypertension but liver showed no significant surface nodularity. Extensive workup elicited negative ANA, anti-smooth ab, anti- soluble liver enzyme, anti- mitochondrial ab, Hep C ab and RNA , HBV DNA, HIV, Hep A IgM, EBV PCR, CMV PCR , Peth level , HSV DNA PCR, HEP C RNA , AFB and normal A1AT. Ferritin was slightly elevated at 506. Due to worsening pancytopenia and rising bilirubin and MELD-NA score of 22, the patient was transferred to our institution. He underwent a trans jugular liver biopsy which was consistent with sinusoidal obstruction syndrome.
Discussion: Sinusoidal occlusion syndrome is a veno-occlusive disease commonly associated with toxic chemotherapy treatments such as oxaliplatin and 5-flurouracil among others (3, 5) . It is also well documented in hematopoietic stem cell transplantation patients who receive myeloablative chemotherapy, and those exposed to toxic alkaloids (3). It is characterized by damage to the sinusoidal endothelium of small hepatic veins which can be affected directly by toxic chemotherapy causing inflammation or by bone marrow myelosuppression of progenitors of endothelial cells which repair sinusoidal lesions (5). With regard to the pyrrolizidine alkaloid toxicity there is evidence in animal models that this can cause alterations in endothelial cells by impacting both endothelial activation and apoptosis, which is thought to be similar to how chemotherapy for metastatic colon cancer causes SOS (5). In CVID, chronic immune cell infiltration of the endothelium by T cells leads to nodular regenerative hyperplasia, which is a well established relationship (2).
Conclusions: X-linked agammaglobulinemia is the most common primary immunodeficiency in the pediatric population which results in repeated serious infections and reactions to vaccinations. It is typically treated with replacement of antibodies through regular Intravenous Immunoglobulin infusions.(4) In the adult population, the most common cause of immunodeficiency is common variable immunodeficiency (CVID) and this is frequently associated with nodular regenerative hyperplasia (2). More studies are needed to identify the pathophysiology of disease in the pediatric counterpart, X-linked agammaglobulinemia (2). In a review of 135 studies of stem cell transplant patients who developed severe sinusoidal obstruction syndrome mortality rates were as high as 84.% (1). More research into clinical correlations, possible treatments and/or modification of risk factors is important because the outcomes in sinusoidal obstruction syndrome can be rapidly fatal, and transplant is not an option as it is in other liver failure etiologies.