Novel BTK Mutation in Patient with Late Diagnosis of X-Linked Agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a genetic disorder with mutation in Bruton’s tyrosine kinase (BTK). Defects in B cell development and immunoglobulin production lead to recurrent infections following loss of maternal IgG at 6 months of age. A 55-year-old male with a longstanding common variable immunodeficiency diagnosis on infusion therapy presented to the clinic with cutaneous T-cell lymphoma, which inspired overall repeat evaluation. Immunoglobulin levels and lymphocyte markers, family history, and genetic testing prompted a true diagnosis of XLA and novel mutation in the BTK gene. Disease-associated mutations have been noted in all five domains of BTK, with missense variants most commonly cited among the 100s of reported genetic alterations. The BTK protein is expressed in hematopoietic lineages and plasma cells, with the exception of T lymphocytes. Disruption in the protein function or absence of BTK halts normal B cell development at the pre-B transitional cell stage and induces premature apoptosis. We present the first reported case of a novel hemizygous BTK c.1492C > G mutation in a patient causing XLA

Posner-Schlossman Syndrome in Common Variable Immunodeficiency

Introduction. Posner-Schlossman syndrome (PSS) is a rare glaucomatocyclitic crisis with clinical features including recurrent episodes of unilateral elevated intraocular pressure. Autoimmune and infectious causes have been proposed as potential etiologies of PSS. We report the first case of PSS in the setting of common variable immunodeficiency (CVID). Case Report. A sixty-two-year-old Caucasian female with a medical history of CVID and ulcerative colitis presented to the emergency room with complaints of acute right-sided vision changes. She reported image distortion, blurriness, and loss of central vision. Physical exam was significant for mildly injected right conjunctiva, visual acuity of 20/70 in right eye, and 20/25 in left eye. The right intraocular pressure was measured at 34 mmHg and left at 12 mmHg. The gonioscopy and dilated fundus examination were unremarkable. Cup to disc ratio was within normal limits, and no afferent pupillary defects were recorded. The patient was acutely treated with three rounds of dorzolamide/timolol and 0.2% brimonidine which decreased the right eye intraocular pressure to 24 mmHg. On follow-up exam with an ophthalmologist, anterior uveitis including an elevated pressure of 41 mmHg on the right and 18 mmHg on the left eye was noted and a PSS diagnosis was confirmed. Conclusion. PSS remains a rare condition with uncertain etiology and no associated systemic conditions. PSS has been postulated to be linked to autoimmune conditions. CVID is associated with many autoimmune disorders including Sjogren’s, rheumatoid arthritis, and colitis. There have been a few reported CVID-associated ocular diseases including granulomatous uveitis and conjunctivitis, chronic anterior uveitis, and birdshot retinopathy. We describe the first case of PSS in a patient with CVID

Serum Sickness

Serum sickness is a type III hypersensitivity reaction. The classic symptoms are malaise, rash, fever, arthralgias, and lymphadenopathy that occur within 8–12 days of antigen exposure and sooner if it is a re-exposure. The diagnosis is based on clinical signs and symptoms with supporting laboratory tests that suggest an inflammatory response in the body with increased immune complex production. This is a self-limiting disease and therapy for serum sickness is primarily supportive to alleviate symptoms using anti-inflammatory medications. Prognosis is very good once the inciting agent has been stopped and rarely does one have permanent end-organ damage as a result of serum sickness. With future research and investigation, there is hope for enhanced risk stratification and earlier detection

Pure Cold-Induced Cholinergic Urticaria in a Pediatric Patient

Cold urticaria and cholinergic urticaria are two distinct entities. The presentation of exclusive cold-induced cholinergic urticaria is very rare. The patient described herein had experienced urticaria in the exclusive setting of exercising in a cold environment. Urticarial testing including laboratory and in-office testing was all negative. The patient has prevented urticaria symptoms with oral antihistamine therapy. Pure cold-induced cholinergic urticaria is rarely described in literature. This form of urticaria has yet to be described in a pediatric patient

Fenugreek Anaphylaxis in a Pediatric Patient

Fenugreek ( Trigonella foenum-graecum) is a food product that belongs to the Leguminosae family along with other legumes. It has been used in India, Greece, and Egypt for culinary and medical purposes since ancient times, and today, fenugreek is used for flavoring foods, dyes, and drugs throughout the world. Many members of the Leguminosae family have been associated with allergies including soybean, green pea, and peanut. Fenugreek is also included in this family and may result in allergic reactions. Two cases of anaphylaxis have been described in children after ingestion of curry and pastes that contain fenugreek, although the true nature of the causative agent was unclear. We report the first case of fenugreek anaphylaxis in a pediatric patient defined by skin testing, immunoglobulin E ImmunoCAP assays, and clear ingestion

Idiopathic Pancreatitis in a Patient with a Mutation

Background Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin infections with abscesses, recurrent pneumonias with pneumatoceles, and immunoglobulin E levels of >10 times the upper limit of normal. Case The patient described herein had a classic case of signal transducer and activator of transcription S (STAT3) deficiency associated with HIES diagnosed several years before this particular presentation. He demonstrated extraimmune manifestations of the disease as well, including characteristic facies and a history of skeletal fractures. In addition, the patient had several distinct episodes of idiopathic pancreatitis for which a full gastrointestinal workup had been performed. STAT3 mutation was confirmed by genotyping at the time of diagnosis of HIES. Conclusions STAT3, a mammalian protein that regulates cell growth, survival, and differentiation, has been linked to human pancreatic carcinogenesis as well as the above-mentioned immune deficiency. Mouse studies demonstrated that genetic ablation of STAT3 exacerbates the course of acute pancreatitis, whereas normal pancreatic STAT3 seems to have a protective effect against necrotizing pancreatitis. An association between STAT3 mutations and pancreatitis has not yet been revealed in humans. Here we describe a case of acute pancreatitis that presented in a patient with STAT3 mutation

Beware of the Caterpillar: Anaphylaxis to the Spotted Tussock Moth Caterpillar,

We present a case report of a 5-year-old boy with presumed anaphylaxis to the caterpillar, Lophocampa maculata, manifesting as the acute development of diffuse urticaria and progressive dyspnea. This reaction required prompt treatment with antihistamines and a bronchodilator. Allergen scratch testing with a homogenized caterpillar extract suggests that immunoglobulin E–mediated type I hypersensitivity as the pathophysiological mechanism responsible for the boy's anaphylaxis. This case report represents the first documented occurrence of an anaphylactic reaction to Lophocampa maculata and adds to the rare incidence of documented hypersensitivity to the order Lepidoptera

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

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