Background:For patients with multiple alloantibodies against red blood cells (RBCs), the challenges posed by transfusion practice are immense due to complex serological reactions that make finding matching units difficult. Identifying underlying antibodies is necessary to prevent hemolytic transfusion reactions (HTRs). Objective:To outline a systematized immunohematologic strategy for the detection and management of several alloantibodies in a surgical patient. Methods:A 64-year-old O-positive female was scheduled for spinal surgery and had a positive pre-transfusion antibody screen. Automated and manual techniques, including multi-cell panels, enzyme-treated cells, thermal amplitude testing, extended phenotyping, DAT, and acid elution, were used in antibody investigation. Results:The alloantibodies anti-s and anti-E were proven to be warm-reactive IgG. The cold-reactive IgM alloantibodies anti-P1 and anti-N were similarly shown to exhibit characteristic temperature reactivity. Anti-Fyb was suspected, but not excluded, for a lack of homozygous rule-in cells. Eluates showed an anti-s reaction with transfused RBCs, consistent with recent exposure. Antigen-negative, phenotype-compatible RBCs were selected that only reacted in the antiglobulin stage, although spin incompatibilities were immediate. Conclusion:This case highlights the significance of systematic approaches to antibody rule-in/rule-out, the thermal-phase test, and phenotype-directed transfusion in patients with multiple alloantibodies. A clear distinction must be made between clinically significant IgG antibodies and cold-reactive IgM antibodies to ensure safe, timely transfusion management.
Background:Serine/threonine kinase 4 (STK4) deficiency is one of the rare causes of combined immunodeficiency (CID). In this study, we report a novel mutation causing STK4 deficiency, which presents with chronic pyelonephritis, an uncommon presentation. Case Presentation:A 10-year-old female with an incidental mass in the kidney extending to the liver, night sweats, and fever was presented. To reduce the mass effect and rule out the possibility of malignancy, the patient underwent a nephrectomy, and a biopsy revealed chronic pyelonephritis. After surgery, due to the persistent leukopenia, the chance of an inborn error of immunity was considered. The patient was referred to the immunology clinic. Investigations:Immunophenotyping revealed low levels of CD3 and CD4. The antibody titer did not show a significant rise after receiving diphtheria and tetanus vaccines. Whole-exome sequencing was performed, and a novel homozygous c.248del, p.Pro83Leufs ∗3 variant was reported in the STK4 gene. The presence of this variant in parents was also confirmed with Sanger sequencing. Conclusion:STK4 deficiency is a rare cause of CID characterized by susceptibility to recurrent infections. Our case shows immune dysfunction manifested as a complex inflammatory syndrome, featuring an abdominal mass that mimics malignancy, expanding the recognized clinical spectrum of this condition.
Drug-induced hypereosinophilic syndromes (HESs) have been associated with a variety of medications, including biologic agents. We present a case of an 85-year-old female with a history of giant cell arteritis (GCA) complicated by ascending aortic aneurysm and aortitis, who developed marked peripheral eosinophilia (peaking at 3710/µL) and a persistent pruritic papular rash during long-term tocilizumab therapy. Extensive infectious, hematologic, and immunologic evaluations were unrevealing. While the clinical picture raised concern for a drug-induced hypersensitivity reaction, histopathology was more consistent with lichen simplex chronicus, and there was no evidence of systemic organ involvement. Her eosinophilia and cutaneous symptoms improved significantly after discontinuing tocilizumab, implicating the drug as a possible trigger. This case highlights the diagnostic challenges in distinguishing drug reaction with eosinophilia and systemic symptoms (DRESS) from other drug-induced or idiopathic dermatoses in patients receiving biologic therapy and underscores the importance of clinicopathologic correlation in guiding management.
Background Griscelli syndrome (GS) is a rare autosomal recessive disorder, characterized by pigmentary dilution of hair and skin. There are three known types of this disease. GS type 1 (GS1), due to mutations in MYO5A , is associated with neurological impairment and hypotonia, while GS type 2 (GS2; RAB27A variants) involves immune dysregulation (hemophagocytic lymphohistiocytosis [HLH]) and GS type 3 ( MLPH variants) causes isolated pigmentary defects. Case Presentation We report a 27‑month‑old Afghan girl, born to consanguineous parents, presenting with developmental delay and hypotonia without the classic silvery hair. A complete evaluation was performed to determine the cause of the developmental delay. Whole exome sequencing revealed a novel homozygous MYO5A variant (c.3508C >T), confirming GS1. Despite the absence of the characteristic silvery hair, microscopic hair examination of the patient showed melanin distribution abnormalities. Conclusion This case highlights the phenotypical variability in GS1 and emphasizes on the importance of considering genetic testing even in atypical presentations. Exploring these novel mutations can expand the known genotype/phenotype spectrum of GS1.
Bee pollen has become an increasingly popular dietary supplement due to potential therapeutic effects. However, ingestion has been shown to trigger allergic responses as severe as anaphylaxis. This case highlights allergic asthma development in a 26-year-old female patient with subsequent anaphylaxis secondary to bee pollen ingestion. This patient presented to the emergency department with complaints of lip and tongue swelling, dyspnea, nausea, abdominal pain, and itching 4 h after bee pollen ingestion. Her medical history included seasonal allergic rhinitis and prior exercise-induced asthma that had not required treatment for 10 years. She was treated with a standard anaphylaxis pharmacological regimen and discharged. The patient then began to experience dyspnea and wheezing 1 month later during peak fall pollen levels. On allergy testing, the patient’s total serum immunoglobulin E (IgE) was elevated at 189 kU/L. She also had elevated specific IgE to common ragweed, mugwort, and cocklebur, which are prominent allergens in the fall. Given the timing of onset of new symptoms, partial relief with an inhaled short-acting B2 agonist, and no pertinent findings for other causes, the patient was subsequently diagnosed with allergic asthma secondary to bee pollen ingestion. Although anaphylaxis to bee pollen is rare, it is becoming increasingly reported in literature and demonstrates an adverse effect that can occur when proper regulation and education are not performed. Dietary supplements like bee pollen need to have further testing and contain more thorough warnings on labels to decrease adverse events and protect people from undue harm.
Dragon fruit, also known as pitahaya, has become increasingly popular in Europe and the United States owing to its nutritional value and potential health-promoting properties. This study describes a patient with anaphylaxis after the ingestion of dragon fruit. We present the case of a patient who experienced a systemic reaction requiring hospitalization 1 h after consuming dragon fruit. His medical history includes allergic rhinitis to Salsola kali pollen. The diagnostic worked-up included prick-by-prick testing with fruits, skin prick testing with aeroallergens, and measurement of specific IgE using ImmunoCAP and ISAC. These tests confirmed sensitization to dragon fruit, several pollens including S. kali, and peach allergens. A protein extract was prepared from dragon fruit pulp. In the protein profile, the most intense bands were observed at 9, 26, and 54 kDa. The patient's IgE recognized multiple bands ranging from 16 to >100 kDa. Immunoblot inhibition demonstrated cross-reactivity: S. kali extract almost completely inhibited IgE recognition of dragon fruit proteins, leaving only faint recognition of a 54-kDa band (identified as catalase), while peach peel extract completely inhibited IgE binding to the dragon fruit extract. In conclusion, sensitization to dragon fruit in this patient was probably due to cross-reactivity with S. kali and peach allergens. This case highlights the potential risks associated with the introduction of novel foods into the diet, particularly in patients previously sensitized to pollen or other plant-derived foods.
Guillain-Barré syndrome (GBS) is a rare autoimmune disorder characterized by peripheral nerve involvement. Among the many kinds of GBS, acute motor axonal neuropathy (AMAN) syndrome has been shown to have distinct clinical characteristics and consequences. Meanwhile, ankylosing spondylitis (AS) is a long-term inflammatory joint illness that mostly affects the sacroiliac joints and the spine; this disorder has been known to cause discomfort and stiffness, which may lead to decreased flexibility over time. Some studies have found a link between anti-TNF α medication and GBS. GBS was commonly related to anti-TNF-α treatment for established AS, which explains the rare overlap of both diseases. In our case, nevertheless, both conditions occurred together without any confirmed therapeutic or infectious provocation. We describe a case of a 35-year-old painter hospitalized with paralysis of the lower and upper limbs but normal reflexes. Electromyography (EMG) demonstrated axonal motor neuropathy, and a lumbar puncture revealed high protein levels (42.2 mg/dL) and a normal cell count, all of which are indicators of GBS; hence, he was diagnosed with AMAN. Additional testing revealed human leukocyte antigen (HLA)-B27 positive and bilateral sacroiliitis on magnetic resonance imaging (MRI), which is consistent with AS. The administration of plasma exchange (PLEX) treatment improved the bulbar function.
Anti-glutamic acid decarboxylase (anti-GAD) autoimmunity possess a poorly understood diversity in the development of neurological manifestations with or without diabetes mellitus (DM) association. A possible genetic contribution might further expand the complexity of anti-GAD pathogenesis and demand further exploration and research. We report three siblings in the same family (two sisters and one brother) who were tested positive for anti-GAD antibodies (anti-GAD-Abs) and presented with different clinical disorders, associated with DM in one of them. Although scarce data are available in the literature concerning the influence of possible genetic predisposition on the development of anti-GAD autoimmunity, yet there is cumulative evidence to support this association which is further elucidated in this report. Whether to recommend family screening tests for patients with positive anti-GAD autoimmunity is still undetermined and further studies are required to solve the unanswered queries pertinent to this potentially treatable autoimmune disorder.
Alpha-gal syndrome (AGS) is an uncommon IgE-mediated allergy to mammalian-derived products, caused by sensitization to the oligosaccharide galactose-α-1,3-galactose (alpha-gal) after tick exposure. Although AGS is best recognized for delayed anaphylaxis following ingestion of red meat, its implications for exposure to mammalian-derived biomaterials remain poorly characterized. We present an elderly woman with AGS who required transcatheter aortic valve replacement (TAVR) using a bovine bioprosthesis. An 84-year-old woman with serologically confirmed AGS following a Lone Star tick bite in 2012 presented with symptomatic severe aortic stenosis. Her clinical history included multiple allergic reactions to beef, persistently elevated IgE to beef, pork, and lamb, and a specific alpha-gal IgE >100 kU/L. Following a multidisciplinary evaluation, she was not considered a candidate for a mechanical valve. A prophylactic regimen was implemented, including cetirizine, omalizumab, and 60 mg prednisone 6 h prior to TAVR. The procedure was successfully performed with a bovine-derived bioprosthetic valve. Perioperative tryptase levels remained within normal range (5.2 µg/L), and no hypersensitivity reactions occurred. Postoperatively, prednisone was tapered, while fexofenadine and omalizumab were continued for 6 months. This case highlights that bioprosthetic valve replacement can be safely performed in AGS patients through multidisciplinary planning and individualized prophylaxis strategies. Further data are needed to develop standardized perioperative management protocols for this rare but clinically significant condition.
ADEM is an inflammatory and demyelinating autoimmune disorder of the central nervous system (CNS). One recognized cause of ADEM is myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). MOGAD affects approximately one in 10,000 people worldwide and is more prevalent in children. Patients typically present with optic neuritis, ADEM, and transverse myelitis. Many patients will experience relapses of demyelinating attacks, and thus, both acute and maintenance therapies are typically used to manage the disease. This case considers an adult female who presented with neurological deficits as a result of MOG-associated ADEM. She had minimal response to traditional therapies but responded well to treatment with IV immunoglobulin (IVIG). This case report explores her clinical course as well as unique clinical significance and conclusions due to the nontraditional use of IVIG.
MyD88 deficiency is an innate immune deficiency that confers susceptibility to bacterial infections, particularly S. pneumoniae, S. aureus, and P. aeruginosa. This autosomal recessive deficiency was first described in 2008 by Van Bernuth et al. Most infections occur before the age of two and can be fatal in 35%. Fever and elevated inflammatory markers are not always present when infection occurs, making the diagnosis difficult. Here, we report two cases within the same family. The first patient presented with peritonitis and liver abscesses due to Pseudomonas aeruginosa infection at 1 month of age, and the second patient had endophthalmitis complicated by bacteremia and meningitis due to Pseudomonas aeruginosa at 20 days of age. These cases highlight the importance of considering MyD88 deficiency in neonates with severe bacterial infections, even without classic inflammatory signs.
Background:Immunoassays are commonly used in clinical laboratories to measure a variety of analytes, including hormones and tumor markers. Interference caused by rheumatoid factor (RF), heterophile antibodies, and human anti-animal antibodies (HAAA) has been reported but is rarely identified in daily practice. Here, we report a case of falsely elevated parathyroid hormone (PTH) due to immunoassay interference and review the literature. Case Presentation:A 57-year-old man who recovered well from lung metastasis of rectal cancer treated with bevacizumab and sintilimab for 1 year, presented to Peking University People's Hospital with persistently high PTH levels (>1200 ng/L) measured by a Roche Elecsys assay. He had hypoadrenocorticism induced by anti-programmed cell death 1 (PD-1), normal renal function, normal total calcium level, and normal 25-OH vitamin D concentration. The Beckman Coulter UniCel DxI 800 and Siemens Immulite 2000 platforms measured PTH levels of 18.3 ng/L and 8.7 ng/L, respectively. After the patient's serum was treated with polyethylene glycol (PEG) precipitation or mouse serum, the PTH levels determined by the Roche immunoassay decreased to 56.5 ng/L and 265.3 ng/L, respectively. Conclusion:Interference due to human anti-mouse antibodies (HAMA) could be the cause of falsely elevated PTH in the patient. Physicians should realize that immunoassay interference can lead to false results and closely communicate with the laboratory to avoid misdiagnosis and inappropriate therapies.
IntroductionThe case report describes a novel finding of a homozygous variant in the coronin 1A (CORO1A) gene, associated with atypical severe combined immunodeficiency (SCID) in a 9-year-old female patient with recurrent infections and unique immunological features, including periodic T-cell lymphocytosis and T- and B-cell lymphopenia.Case History and ExaminationA 9-year-old female with a known history of recurrent pneumonia presented to the emergency department with a 2-week history of intermittent fever, progressive lethargy, and pallor. Her past medical history was remarkable for multiple hospital admissions secondary to community-acquired pneumonia and urinary tract infections, totaling four admissions to date. Family history was significant for consanguinity between parents and a healthy 4-year-old younger male sibling. Chest computed tomography (CT) demonstrated bilateral diffuse centrilobular nodules, scattered ground-glass opacities, and left lower lobe consolidation, in addition to a tree-in-bud pattern. Immunological evaluation revealed T-cell lymphocytosis, B-cell lymphopenia, and a decreased CD4/CD8 ratio. Based on these findings, the pediatric allergy and immunology team recommended genetic testing for primary immunodeficiency. The panel identified a homozygous variant of uncertain significance (VUS) in the CORO1A gene. Pathogenic variants in CORO1A are associated with autosomal recessive CORO1A-related SCID.ConclusionThe novel homozygous variant in the CORO1A gene suggests the likelihood of an atypical form of SCID, characterized by periodic T-cell lymphocytosis, T-cell lymphopenia, B-cell lymphopenia, and a low CD4/CD8 ratio, expanding the spectrum of CORO1A deficiency.
We report a novel homozygous PRF1 variant, PRF1 (NM_001083116.3):c.343G > A (p.Glu115Lys), identified by whole-exome sequencing (WES) in an 11-year-old girl with atypical familial hemophagocytic lymphohistiocytosis (FHL). The variant, inherited from asymptomatic heterozygous parents, was absent or extremely rare in population databases and was predicted to be deleterious by multiple in silico tools. Born to consanguineous parents, the patient presented with recurrent fever, pancytopenia, and multiorgan failure following SARS-CoV-2 infection, further complicated by Epstein-Barr virus (EBV) and cytomegalovirus (CMV) coinfections. Despite intensive immunosuppressive therapy, she developed seizures, an intracranial hemorrhage, and died at age 11. A striking family history of unexplained febrile deaths in infancy and childhood strongly supported autosomal recessive inheritance. It emphasizes the role of viral triggers, especially COVID-19, in revealing genetic predispositions and underscores the importance of genetic screening in atypical cases.
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defective phagocyte oxidative burst and may present in early life with severe or recurrent infections. We report a female infant born at 38 weeks’ gestation (birth weight 2700 g) who developed fever and presumed sepsis at 5 days of life, followed by multiple recurrent hospitalizations for febrile illness with suspected meningitis, diarrhea, dehydration, and failure to thrive. Cerebrospinal fluid (CSF) evaluations across episodes demonstrated pleocytosis with elevated protein and normal-to-low glucose, while Gram stain and CSF cultures were repeatedly negative, consistent with recurrent culture-negative meningitis. Laboratory assessment showed intermittent anemia, thrombocytosis, and episodes of significant neutropenia. Complement and immunoglobulin levels were within reference ranges, and flow cytometry demonstrated preserved T- and B-lymphocyte compartments. A flow cytometric dihydrorhodamine (DHR) oxidative burst assay was markedly abnormal (phorbol 12-myristate 13-acetate stimulation index 13%; Escherichia coli stimulation index 22.3%), supporting the diagnosis of CGD. At ~4.5 months of age, a sterile catheter urine culture grew multidrug-resistant Klebsiella pneumoniae at ≥100,000 CFU/mL with susceptibility limited to aminoglycosides; the patient was treated with amikacin 15 mg/kg/dose intravenously once daily for 10 days, with defervescence within 48 h, clinical recovery, and a repeat urine culture showing no growth. Genetic testing was not performed due to financial and social constraints, and longer-term outcomes beyond early infancy were unavailable in the record extract. This case underscores that recurrent culture-negative meningitis in early infancy should prompt evaluation for primary immunodeficiency and that early DHR testing can expedite CGD diagnosis and guide timely preventive management and specialist referral.
Purpose:This study aims to present the diagnostic and therapeutic challenges of Cogan's syndrome (CS) and the outcomes of hearing rehabilitation in long-term follow-up. Methods:Retrospective data analyses of patients with CS treated at Semmelweis University were performed. Comprehensive evaluations, including medical assessments, audiological measurements, otoneurological investigations, imaging, and ophthalmological examinations, were conducted on all patients. Results:Between 1995 and 2022, five patients with CS were followed. The severity and timing of ear and ocular symptoms varied. Bilateral, asymmetric hearing impairment manifested as sudden sensorineural hearing loss, and all patients experienced loss of bilateral vestibular function. Various ophthalmological manifestations showed instability over time. Systemic corticosteroids were the first-line treatment, immunosuppressive therapy (methotrexate, cyclophosphamide, cyclosporin A), and biological treatment (infliximab, adalimumab) used as second- and third-line therapies. Eye symptoms of all five patients were controlled by medications. For hearing impairment, four patients were treated with cochlear implantation and achieved long-term stable speech perception. Hearing improvement was found in one patient by conservative therapy. One patient required reimplantation due to device failure, which was performed without complications. Conclusion:Sudden hearing loss and vestibular attacks in young patients require thorough investigation and close follow-up. Early corticosteroid therapy or immunosuppressive and biological treatment can stabilize symptoms, including hearing levels. Early hearing rehabilitation with cochlear implants is crucial. Long-term follow-up indicates stable hearing levels and speech perception.
Multiple sclerosis (MS) is a chronic autoimmune disease and demyelinating disorder of the central nervous system (CNS) with diverse clinical presentations that can make the diagnosis challenging. In this case report, we describe a rare initial presentation of MS, mistaken for Type 1 diabetes mellitus (T1DM) impaired gastric motility. The patient is a 32-year-old female with a history significant for T1DM who presented with 3 days of intractable vertigo, nystagmus, and gait disturbance. She was discharged 2 days prior for intractable nausea and vomiting presumed to be due to impaired gastric motility called gastroparesis. There was no prior history of focal neurologic deficits. Her family history revealed extensive autoimmune diseases in multiple first-degree relatives. Physical examination suggested a peripheral lesion but could not rule out a central lesion. Magnetic resonance imaging (MRI) brain demonstrated white matter lesions in regions specific for MS. The patient experienced modest improvement with IV corticosteroids. Patients with T1DM have a threefold increase in the incidence of MS. While gastroparesis is an uncommon initial symptom of MS, this diagnosis should be considered, particularly when neurological deficits are present. This case underscores the importance of considering the enteric nervous system in patients with preexisting autoimmune conditions with new-onset neurological symptoms.
Background:Leukocytoclastic vasculitis (LCV) is a known hypersensitivity reaction to biologic agents, often linked to tumor necrosis factor-α (TNF-α)inhibitors. We present a rare case of LCV in a patient receiving tocilizumab, a monoclonal antibody directed against interleukin-6 (IL-6)receptor. Case presentation:A 33-year-old Asian female with seropositive rheumatoid arthritis presented to the rheumatology clinic complaining of a new rash that started a few days after an infusion of tocilizumab. Her rheumatoid arthritis had been managed with upadacitinib for several years, which was discontinued due to persistent transaminitis. She was started on tocilizumab after a 4-month break from biologics. Following the first tocilizumab infusion, she recalled having transient fatigue and several red dots on her forearms and feet. A few days after the second infusion, she developed a purpuric rash on her lower extremities and forearms. Skin biopsy confirmed LCV. The rash resolved slowly in a month after discontinuation of tocilizumab and prescription of prednisone 20 mg daily. At her 3-month follow-up, the patient remained in remission, and her rheumatoid arthritis was uneventfully managed with abatacept. Conclusions:While most cases of biologic-associated LCV are induced by TNF-α inhibitors, only two known cases of tocilizumab-induced hypersensitivity vasculitis have been published in the literature. Our case represents only the third reported instance in the literature, highlighting the need to raise awareness of tocilizumab as a potential cause of leukocytoclastic vasculitis and the importance of prompt recognition and management.
This case report describes a 67-year-old male who presented with a 2-month history of painless left eye redness and muffled hearing. Ophthalmologic examination revealed elevated intraocular pressure (IOP) and significant conjunctival injection without associated pain or visual disturbance. Blood was observed in Schlemm’s canal (SC), and a thorough investigation for elevated episcleral venous pressure (EVP) was performed. Imaging, including magnetic resonance imaging (MRI) and cerebral angiogram, was unremarkable. A rheumatologic workup led to the diagnosis of granulomatosis with polyangiitis (GPA). The patient’s ocular symptoms improved significantly with systemic steroid treatment. He was subsequently managed with rituximab and avacopan as per standard GPA therapy. This case highlights the importance of considering vasculitis in patients presenting with unexplained elevation of EVP, and painless scleritis, particularly when there are also extraocular complaints.
