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Common Variable Immunodeficiency Presenting with Recurrent Ascending Cholangitis Treated with Oral Immunoglobulins

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Scholar: Pilot and Validation Studies ISSN: 2689-7644 Volume 1 Issue 1 Pages: 11 - 13 DOI:10.32778/SPVS.71366.2020.3 Common Variable Immunodeficiency Presenting with Recurrent Ascending Cholangitis Treated with Oral Immunoglobulins Authors: Marija Rowane, OMS1, Jaimin Patel, DO2, Tina Abraham, DO3, Jason Schend, DO4, Robert Hostoffer, DO, LhD, MMedEd, FAAP, FACOP, FACOI, FCCP5 Affiliations: 1) Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio; 2) Department of Internal Medicine, Lehigh Valley Health Network, Allentown, Pennsylvania; 3) Pulmonary Allergy Critical Care & Sleep Associates, Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/11/2409933/i2689-7644-1-1-11.pdf by guest on 27 September 2021 Rochester Hills, Michigan; 4) Department of Pulmonary Critical Care, University Hospitals Cleveland Medical Center, Cleveland, Ohio; 5) Allergy Immunology Associates, Inc., Mayfield Heights, Ohio Keywords: Common Variable Immunodeficiency, primary immune deficiency disorder, ascending cholangitis, oral immunoglobulin, hepatobiliary, gastrointestinal Abstract: Background: Common variable immunodeficiency (CVID) is a heterogeneous group of primary immune deficiency disorders that may be characterized by heightened susceptibility to gastrointestinal (GI) infection. GI conditions manifest in 20 to 50% of CVID patients but rarely include cholangitis. Methods/Results: This is a 61-year-old female, with a history of cholecystectomy and gastric bypass, who presented with recurrent ascending cholangitis for eight years. After a hepaticojejunostomy to correct a bile duct stricture complication from the cholecystectomy, ascending cholangitis was diagnosed by clinical presentation of fever and right upper quadrant pain and imaging revealing pneumobilia. CVID was diagnosed after no response to pneumococcal polysaccharide vaccine, as well as serum IgA and IgG measured below the normal ranges. The patient was prescribed a successful, weekly regimen of 15 g of oral intravenous immunoglobulin (IVIG) ten percent liquid (Gammaplex® 10%, 5 gm/50 mL). Conclusion: Oral human IVIG is a novel treatment and has been infrequently utilized for management of chronic rotavirus, necrotizing enterocolitis, diarrhea, HIV enteropathy, irritable bowel syndrome, and malnutrition. This is the first case of recurrent ascending cholangitis as the primary manifestation of CVID, as well as successful treatment of this condition with oral IVIG, in the literature. Article History: Date received: 06/07/2019 Date accepted: 08/04/2019 Corresponding Author: Marija Rowane, OMS E-mail: [email protected] Introduction: lymphoma, and cholangitis.2-5 Three studies have Common variable immunodeficiency reported associations of cholangitis and CVID or (CVID) is a heterogeneous group of primary primary immunodeficiences,3-5 although we report immune deficiency disorders (PIDD) characterized the first case of recurrent ascending cholangitis as by heightened susceptibility to the primary manifestation of CVID. In addition, this hypogammagloblunemia, insufficient vaccination case demonstrated the first reported successful responses, autoimmune and non-infectious treatment of this condition with oral human inflammatory co-morbidities, and sinopulmonary intravenous immunoglobulin (IVIG). and gastrointestinal (GI) infections.1 GI conditions A 61-year-old female with a history of manifest in 20 to 50% of CVID patients and include cholecystectomy and gastric bypass presented with esophageal candidiasis, diarrhea, nodular lymphoid recurrent ascending cholangitis every other week for hyperplasia, autoimmune enteropathy, irritable eight years. After a hepaticojejunostomy to correct a bowel disease-like colitis, pernicious anemia, gastric bile duct stricture complication from the adenocarcinoma, B cell immunophenotype cholecystectomy, the patient had been experiencing 11 Ascending Cholangitis Treated with Oral IVIG ISSN: 2689-7644 Volume 1 Issue 1 Pages: 11 - 13 DOI:10.32778/SPVS.71366.2020.3 recurrent episodes of right upper quadrant (RUQ) properties of Ig fragment enable sustained active pain with fever. Over a 10-month period, the patient binding and reduced bacterial enterotoxin, had been prescribed seven courses of oral endotoxin, and exotoxin activity.7 However, further antibiotics, including ciprofloxacin and controlled studies are necessary to investigate the metronidazole. These were increased to three per optimal dose and mechanisms of this novel route of course, followed by biweekly regimens. Ascending IVIG administration. cholangitis was diagnosed by fever and RUQ pain in PIDD GI or hepatobiliary complications the clinical presentation and supported by CT and may manifest as infections, autoimmune MRI imaging revealing pneumobilia. phenomena, unregulated inflammatory conditions, Both serum IgA and IgG measured below malignancies, and diseases secondary to therapeutic Downloaded from http://meridian.allenpress.com/scholar/article-pdf/1/1/11/2409933/i2689-7644-1-1-11.pdf by guest on 27 September 2021 the normal ranges, at 58 mg/dL (normal range, 70- intervention.2 GI conditions are reported in up to 400 mg/dL) and 571 mg/dL (normal range, 700- 50% of CVID patients, with infectious diarrhea as 1600 mg/dL), respectively. The pneumococcal the most common symptom.1,3 Gastric vaccination did not elicit a serologic response. adenocarcinoma, immune-mediated enteropathy, Alkaline phosphatase (ALP, 216 U/L) and alanine nodular lymphoid hyperplasia of the GI tract, small aminotransferase (ALT, 82 U/L) levels were above intestine bacterial overgrowth, small bowel villous the normal limits. atrophy, and gastritis have also been noted in CVID The patient began a weekly regimen of 15 g cases.1 Hepatic manifestations, most commonly of oral IVIG ten percent liquid (Gammaplex® 10%, hepatitis and liver granulomas, are less frequent but 5 gm/50 mL). After the first two courses of oral have been documented in 9 to 12% of patients with IVIG, the patient did not experience symptoms of CVID.1,3 Autoimmune liver diseases, such as cholangitis. She continued this treatment plan primary biliary cirrhosis and autoimmune hepatitis, without return of symptoms. and nodular regenerative hyperplasia (NRH) are rare but have also been noted in the literature.3 Discussion: There are sparse publications reporting International interest in utilizing oral human, hepatobiliary manifestations of CVID, such as bovine, or chicken egg–derived Ig for prophylaxis cholangitis.3-5 Mahdavinia et al. described the first and treatment of childhood malnutrition and two CVID cases associated with primary sclerosing gastrointestinal conditions, emerged several decades cholangitis (PSC), an inflammatory autoimmune ago.6 Several studies preventing necrotizing liver disease of chronic biliary epithelium causing enterocolitis or managing rotavirus diarrhea offer chronic cholestasis, multifocal bile duct strictures, evidence of reduced symptoms through this novel and potential complications of cirrhosis and route of administration.6 Losonsky et al. reported malignancy.3 A 66-year-old male presenting with approximately 25% recovery of chronic diarrhea or pruritus and elevated liver enzyme was diagnosed rotavirus, as well as recovered immunological with PSC, supported by endoscopic retrograde activity in three children with unspecified immune cholangiopancreatography and liver biopsy.3 After a deficiency.7 decade of recurrent urinary tract infections, Due to its antigen-neutralizing activity and Clostridium difficile, ulcerative colitis, pneumonias, anti-inflammatory property, orally administered Ig low immunoglobulin titers and negative PPSV23 may lower risk of systemic allergic response, confirmed a CVID diagnosis.3 Mahdavinia et al. also hematological diseases, and endotoxin absorption.6-7 detailed a 29-year-old female CVID patient with a Oral Ig may improve intestinal barrier function and, history of recurrent sinopulmonary, urinary tract, thus, prevent increased permeability, which may and giardia infections, presenting with pruritus, manifest in severely ill patients with higher fatigue, and elevated liver enzymes. Magnetic susceptibility to endotoxemia and sepsis.6 Most resonance cholangiopancreatogram and liver biopsy studies assessing effectiveness of orally-administered verified a PSC diagnosis.3 Both CVID cases were Ig (particularly IgG) from human or bovine serum managed with IVIG.3 Germinaro et al. documented indicate resistance of degradation from gastric acid a CVID case diagnosed after presentation of and proteolytic enzyme exposure.7 The physical hypogammaglobulinemia and numerous episodes of 12 Ascending Cholangitis Treated with Oral IVIG ISSN: 2689-7644 Volume 1 Issue 1 Pages: 11 - 13 DOI:10.32778/SPVS.71366.2020.3 pneumonia, sinusitis, and cholangitis.4 IVIG and References: later subcutaneous IgG treatment significantly 1. Ebert S, Bracken S, Woosley J, Greene KG, Hansen reduced the frequency of infections.4 A study by J, Lobo J, et al. Common variable immunodeficiency Pikkarainen et al. investigated the gastrointestinal (CVID). Rare Rheumatic Diseases of Immunologic phenotype of CVID in a cohort of 105 Finish Dysregulation. 2019;59-85. patients, five of which were diagnosed with PSC or 2. Al-Muhsen SZ. Gastrointestinal and hepatic manifestations of primary immune deficiency CVID-associated cholangitis.5 The present report of diseases. Saudi J Gastroenterol [Internet]. 2009 [cited recurrent ascending cholangitis is the first 2019 Aug 16];16(2):66-74. Available from: specifically
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