Atypical Infection Research Articles

Case report: HSV lymphadenitis in immunocompromised patient with CLL

BackgroundRichter’s transformation (RT) in chronic lymphocytic leukemia (CLL) is associated with poor prognosis and requires prompt modifications in patient care. CLL patients are susceptible to severe infections due to immune dysregulation induced by their malignancy and immunosuppressive therapies.Case presentationWe present a case of a 63-year-old man with CLL who previously achieved remission and presented with a right inguinal mass. He was diagnosed with Rai Stage I CLL with del6q, without TP53 mutation, and treated with 6 cycles of fludarabine, cyclophosphamide, and rituximab (FCR) 6 years prior. Transformed CLL was suspected based on his lymphadenopathy, elevated lactate dehydrogenase, and constitutional symptoms, but excisional biopsy unexpectedly revealed herpes simplex virus (HSV)-1 and HSV-2, indicating a diagnosis of HSV lymphadenitis concurrent with CLL relapse with no transformation but acquisition of 17p deletion consistent with clonal evolution. The patient received three courses of dexamethasone and acyclovir, leading to successful clearance of the infection, evidenced by the resolution of his B symptoms. Subsequently, he was treated for the CLL recurrence with rituximab and venetoclax, demonstrating a favorable response with significant improvement in adenopathy and resolution of lymphocytosis.DiscussionThis case highlights the possibility of reactivated dormant viral infections in the context of CLL relapse, underscoring the importance of comprehensive evaluation in CLL patients presenting with lymphadenopathy. Due to immunosuppressive defects and iatrogenic hypogammaglobulinemia, patients with CLL face an increased risk of viral infections, with HSV reactivation occurring more frequently and severely in the setting of hematologic malignancies and dysregulated T-cell immunity. Timely administration of antiviral therapy is crucial for HSV lymphadenitis to prevent rapid progression and debilitating symptoms. This case demonstrates the importance of considering atypical viral infection presentations in CLL patients and emphasizes the necessity of timely and adequate biopsies to differentiate between CLL transformation, HSV lymphadenopathy, and other causes of lymphadenopathy while avoiding unnecessarily aggressive lymphoma therapy.

The emerging role of photodynamic therapy in the treatment of cutaneous infections.

Cutaneous infections pose ongoing challenges to standard treatments due to resistance and limited efficacy. Photodynamic therapy (PDT) emerges as a promising supplement or an alternative to address complicated cases. In this review, we comprehensively review PDT's safety and efficacy in treating cutaneous infections. A PubMed systematic review with search terms for PDT treatment, hair, skin, and nail infections. There were a total of 43 studies on the use of PDT in cutaneous infections which discussed the treatment of viral (N.=20), bacterial (N.=11), fungal (N.=9), and protozoal (N.=3) infections. There is evidence for using PDT, mostly 5-aminolevulinic acid (5-ALA) and methyl aminolevulinate (MAL), in the treatment of cutaneous infections. Most evidence for viral infections involved treatment with 5-ALA PDT in condyloma acuminatum (CoAc), verruca vulgaris, and molluscum contagiosum. In bacterial infections, 5-ALA and MB PDT have been used to achieve complete remission in refractory Pseudomonas and atypical mycobacteria infections without recurrence. In onychomycosis, MAL PDT achieved a 40.9% cure rate and MB PDT showed a 77.8-100% cure rate with no reports of recurrence. Parasitic infections, such as leishmaniasis have also been successfully treated with both 5-ALA and MAL PDT. PDT is a promising treatment option for cutaneous infections, with growing evidence for its utility in treating cutaneous bacterial, viral, fungal, and parasitic infections, particularly those that fail standard treatments. Side effects were mostly limited to localized pain with good outcomes and low recurrence rates.

Atypical delayed ventriculoperitoneal shunt infection following hysteroscopic polypectomy: illustrative case.

A 36-year-old female with a history of congenital hydrocephalus, treated with ventriculoperitoneal (VP) shunt placement at 3 months of age and a shunt revision at 9 years of age, presented with erythema, induration, and drainage of an abdominal incision through which the distal catheter of her VP shunt had been implanted many years prior. She had no recent risk factors for infection apart from a minor transvaginal gynecological procedure that involved hysteroscopy with dilation and curettage for uterine polyps. Abdominal wound cultures grew Cutibacterium acnes, Corynebacterium species, and Mycobacterium chelonae. She was managed with initial externalization, followed by complete explantation of her shunt system following a successful clamp trial; in tandem, the atypical polymicrobial infection was treated with a prolonged regimen of intravenous antibiotics followed by oral antibiotics and close monitoring of the wound, which healed appropriately. Although the majority of shunt infections occur due to a characteristic set of organisms within an expected time frame, this case emphasizes the importance of a thorough workup and follow-up for shunt-treated patients with potential infections-even when they fall outside the usual window or have an atypical presentation-for the possibility of uncommon infecting organisms. https://thejns.org/doi/10.3171/CASE24472.

The carpal tunnel syndrome caused by Arthrinium phaeospermum infection: first case report and literature review

BackgroundThe carpal tunnel syndrome (CTS) caused by atypical infection is a therapeutic and diagnostic challenge. Atypical clinical presentations often lead to misdiagnosis and incorrect therapy.Case presentationThis article reports a case of deep infection leading to CTS manifestations. A male patient was admitted for numbness and pain of the left hand. Left carpal tunnel release, median nerve decompression with synovial resection were performed. Inflamed synovium and effusion were submitted for bacterial culture and metagenomic next-generation sequencing (mNGS). The etiologic agent was identified as Arthrinium phaeospermum and the patient recovered after surgical debridement and 10 months of therapy.ConclusionsDiagnosis of mycotic infection of the hand is challenging as the presentation is similar to other conditions. mNGS is presented as a valuable diagnostic adjunct for uncovering unusual infectious agents.

A case report of Penicillium chorioretinitis in a Border Collie dog

Systemic fungal pathogens typically gain entry through a single portal and disseminate to affect multiple body systems. Infections caused by fungal Penicillium species are rare in dogs, and these cases have a poor prognosis. An unknown Penicillium species was isolated from the right eye of a middle‐aged Border Collie without evidence of systemic disease. Due to financial limitations, an extensive diagnostic evaluation could not be performed. Histopathology alone failed to identify the specific causative agent; however, fungal culture on aqueous humor provided the definitive diagnosis. This case highlights the advantage of collecting ocular fluids after enucleation to diagnose atypical fungal infections.

When is it a sexually transmitted infection? Intimate contact transmission of pathogens not traditionally defined as STIs

Purpose of review Several microorganisms, which are not traditionally considered sexually transmitted infections (STIs), are capable of sexual transmission and have the potential to cause global outbreaks. The aim of this review is to describe pathogens which are not traditionally defined as STIs, to grant insight on current and potential outbreaks and call for clinical vigilance among members of key populations. Recent findings Recent findings emphasize that several pathogens, not traditionally classified as STIs, can be sexually transmissible. These include the mpox virus, enteric infections such as Shigella spp., dermatophytes such as Trichophyton mentagrophytes, ectoparasites and atypical bacterial genito-urinary infections such as Neisseria meningitidis. The internationally reported outbreaks and the reports on potential sexual transmission of these pathogens underlines the emerging risks, the need for a broader STI definition and the importance of vigilant public health control strategies. Summary These findings suggest that clinical practice should broaden STI testing and awareness to include pathogens not traditionally considered sexually transmissible, particularly among key populations. Clinicians must be vigilant for atypical presentations, ensuring comprehensive sexual healthcare and diagnostic testing. Development of targeted preventive efforts and continuous surveillance to detect and manage emerging sexually transmissible infections is paramount.

Leishmaniasis masquerading as pyoderma gangrenosum in a non-endemic area: A case report.

Pyoderma gangrenosum (PG) can be difficult to diagnose, leading to diagnostic delay which affects patient outcomes and increases health care utilization. Among different scenarios of diagnostic delay, atypical infections can mimic PG. Here, we present a case of extensive cutaneous leishmaniasis initially misdiagnosed as the superficial granulomatous variant of PG and describe diagnostic clues to aid in differentiation.

Primary cutaneous infections with non-tuberculous mycobacteria: a report of 6 cases

BackgroundThe incidence of non-tuberculous mycobacterium infection has shown a gradual increasing trend in recent years, among which cutaneous manifestations as an important aspect. This study aimed to describe the clinical features and microbiological findings in 6 cases of primary cutaneous nontuberculous mycobacterium infection.MethodsIn this retrospective study from June 2021 to June 2022, the clinical data and microbiological results of six cases diagnosed with primary cutaneous non-tuberculous mycobacterium infection in department of dermatology, Hangzhou Third People’s Hospital were analyzed.ResultsAll six cases were primary cutaneous non-tuberculous mycobacterium infections, four of which had a history of trauma or exposure, and two had an underlying disease that could lead to compromised immunity. All patients presented with erythema nodular skin lesions, four on the upper or lower extremities, one on the face, and one on the right hip. The histopathological findings of five patients who underwent biopsy were granulomatous inflammatory changes with mixed infiltration. Laboratory cultures using tissue or tissue fluid were all successful, including four Mycobacterium marinum, one Mycobacterium abscessus, and one Mycobacterium avium. Metagenomics next-generation sequencing detected results consistent with culture colonies in only two cases. With the exception of case 4, all patients responded well to oral medication, with a course of treatment ranging from 4 months to 1 year, and the prognosis was good.ConclusionsThe clinical features of primary cutaneous non-tuberculous mycobacterium infection are often lacking in specificity, and the identification of related strains is difficult for a variety of reasons. Although the results of metagenomics next-generation sequencing are useful for pathogen spectrum identification, its diagnostic value should be carefully reevaluated under certain circumstances. Patients with suspected triggers who do not respond well to conventional treatments should be suspected as atypical infection and potential immunosuppression. If diagnosed and treated promptly, the prognosis of primary cutaneous non-tuberculous mycobacterium infection is generally good.

Community-Associated MRSA—Not So Innocent Sibling per Se: A Case Report

Background: Methicillin-resistant S. aureus (MRSA) is a major healthcare burden and is classified as healthcare-associated (HA-MRSA) and community-associated (CA-MRSA). While HA-MRSA is clinically feared, CA-MRSA is often considered less pathogenic. This case report highlights the serious course of illness due to CA-MRSA infection and provides a treatment strategy for the management of such cases. Case description: A 41-year-old male presented with fever and breathlessness for five days. Upon admission, he was provided empirical treatment for atypical infections and vasopressor support for hypotension. His condition deteriorated, necessitating ventilator support. Although the initial tracheal Bio Fire test indicated MRSA, his clinical manifestations did not match MRSA pneumonia symptoms; however, CA-MRSA was confirmed within 12 h. Skin legions developed within 16 h and progressed gradually from ecchymosis, petechial, and palpable purpura to bullous lesions over 72 h. The antibiotic regimen was modified and optimized with the addition of Clindamycin, Vancomycin, and Meropenem–Colistin. Owing to high IL-6 levels, dual vasopressor support, and acute kidney failure, he was started on early (within 12 h) continuous renal replacement therapy (CRRT) with CytoSorb filter (for 3 days) for cytokine removal. IL-6 levels decreased after two days of CytoSorb use. Subsequently, the patient stabilized with reduced dependence on vasopressor and ventilator assistance. Discussion: Early diagnosis of CA-MRSA and management with CRRT using CytoSorb may help improve patient outcomes. To our knowledge, this is the first report of clinical management of CA-MRSA with CytoSorb therapy in India that resulted in positive outcomes.

Exploring stakeholder perceptions about using artificial intelligence for the diagnosis of rare and atypical infections.

To evaluate critical care provider perspectives about diagnostic practices for rare and atypical infections and the potential for using artificial intelligence (AI) as a decision-support system (DSS). We conducted an anonymous web-based survey among critical care providers at Mayo Clinic Rochester between 11/25/2023 and 1/15/2024, to evaluate their experience with rare and atypical infection diagnostic processes and AI-based DSSs. We also assessed the perceived usefulness of AI-based DSSs, their potential impact on improving diagnostic practices for rare and atypical infections, and the perceived risks and benefits of their use. A total of 47/143 providers completed the survey. 38/47 agreed that there was a delay in diagnosing rare and atypical infections. Among those who agreed, limited assessment of specific patient factors and failure to consider them were the most frequently cited important contributing factors (33/38). 38/47 reported familiarity with the AI-based DSS applications available to critical care providers. Less than half (18/38) thought AI-based DSSs often provided valuable insights for patient care, but almost three quarters (34/47) thought AI-based DDSs often provided valuable insight when specifically asked about their ability to improve the diagnosis of rare and atypical infections. All respondents rated reliability as important in enhancing the perceived utility of AI-based DSSs (47/47) and almost all rated interpretability and integration into the workflow as important (45/47). The primary concern about implementing an AI-based DSS in this context was alert fatigue (44/47). Most critical care providers perceived that there are delays in diagnosing rare infections, indicating inadequate assessment and consideration of the diagnosis as the major contributors. Reliability, interpretability, workflow integration, and alert fatigue emerged as key factors impacting usability of AI-based DSS. These findings will inform the development and implementation of an AI-based diagnostic algorithm to aid in identifying rare and atypical infections.

Chronic dacryocystitis due to Mycobacterium abscessus.

Dacryocystitis, inflammation and infection of the lacrimal sac, is most commonly caused by infection from Staphylococcus and Streptococcus species. This report highlights a rare case of chronic dacryocystitis due to the atypical pathogen Mycobacterium abscessus. A 62-year-old woman presented with several months of left medial canthal pain, tenderness, and discharge. Exam demonstrated a left tender medial nodule, and imaging showed left lacrimal sac dilation and fluid collection consistent with dacryocystitis. She underwent external dacryocystorhinostomy with drainage and culture of the abscess, which was positive for M. abscessus. Her post-surgical treatment required an extended course of antibiotics, including omadacycline and azithromycin, with slow but progressive symptomatic improvement. This case is only the second reported case of dacryocystitis due to M. abscessus and suggests a role for culturing lacrimal sac abscesses intraoperatively due to the need for extended antibiotic therapy for atypical infections that may have high antibiotic resistance.

Prolonged eosinophilia caused by Strongyloidiasis in a patient with rheumatoid arthritis treated with Upadacitinib.

Rheumatoid arthritis (RA) is a systemic disease, which is caused by dysregulation of the immune system in the susceptible persons, making them immunocompromised and prone to infections during the course of their disease. The majority of RA patients are being treated with immunosuppressive drugs which render them even more immunocompromised. We present a Caucasian patient living in South-eastern Europe who developed prolonged eosinophilia during the treatment of RA with upadacitinib. After a comprehensive work-up she was diagnosed with Strongyloidiasis although living in non-endemic region of the world. We emphasize the importance of regular follow-up of immunocompromised patients and raise awareness of not only typical but also atypical infections which can occur during the course of the disease.

Curcumin Alleviates Airway Inflammation in Cough-Variant Asthmatic Rats by Modulating M1/M2 Macrophage Polarization.

With the increase of environmental pollution and atypical pathogen infections, the incidence of cough variant asthma (CVA) has been increasing annually, making it a pressing issue of the medical community. This study aims to observe the ameliorative effect of curcumin on a rat model of cough variant asthma. A rat model of cough variant asthma was induced by sensitization with ovalbumin combined with aluminum hydroxide (Al(OH)3), followed by repeated excitations. The drug was administered on the day of the initial nebulized attack, and gavage was administered for 14 d. Pathological changes in the lung tissues were observed, along with the assessment of cough susceptibility and airway resistance. The number of inflammatory cell eosinophils and leukocytes were determined in alveolar lavage fluid. Additionally, serum inflammatory factors and lung tissues Matrix Metalloproteinase-9 (MMP-9) protein were assessed. The level of M1/M2 macrophages was also detected. Following the administration of curcumin, there was reduced inflammatory infiltration, less disordered arrangement of the lung tissue, and decreased abnormal proliferation of lung tissues in cough variant asthma rats compared to the model group. Curcumin treatment led toa notable reduction in cough frequency, a significant decrease in pro-inflammatory factor concentration levels in serum and inflammatory cell counts in the alveolar lavage fluid, and a marked increase in anti-inflammatory factor levels (p < 0.05). Additionally, curcumin administration led to a significant increase in M2-type macrophage levels, while simultaneously decreasing the levels of M1-type macrophages (p < 0.05). The administration of curcumin effectively ameliorates ovalbumin-induced airway inflammation in cough-variant asthma rats. This effect is attributed to modulating macrophage polarization towards the anti-inflammatory M2 phenotype, thereby reducing airway inflammation, airway hyperresponsiveness, and lung tissue injury.

Hypogammaglobulinemia in a child with atypical hemolytic-uremic syndrome

We present a unique clinical case of an atypical hemolytic-uremic syndrome in a child. The mutation in exon 6 of the CD46 gene (chr1:207940532G&gt;C) leads to a homozygous or hemizygous missense substitution. An 8-year-old girl was urgently hospitalized with symptoms of hemorrhagic syndrome and acute kidney injury. The child from the second pregnancy with an aggravated obstetric anamnesis, the first operative labor at the 38th week, who has an aggravated genealogical anamnesis. Initially, the disease developed in the guise of gastroenterological pathology: the girl had dyspeptic disorders, most likely associated with pathology of carbohydrate metabolism, also frequent infectious diseases and a lag in physical development. From the age of 4 years, the girl suffered from persistent hypoalbuminemia, hypoproteinemia and hypogammaglobulinemia, requiring replacement therapy with intravenous immunoglobulins. She was repeatedly examined in gastroenterological departments in Yekaterinburg and Moscow in 2021-2023, but no data concerning protein-losing enteropathies or primary immunodeficiency was obtained. Also, the whole-exome sequencing with result validation hasn’t confirmed an inherited etiology of the presumed congenital immune error. However, a CD46 gene mutation, associated with the development of hemolytic-uremic syndrome in some publications, was identified in the study. The signs of thrombotic microangiopathy were preceded by fever of unspecified etiology: microangiopathic hemolysis, thrombocytopenia, hyperazotemia, C3 consumption, proteinuria, and macrohematuria; hypercholesterolemia, protein metabolism disorder, increased transaminases, ferritin were also noted. According to the ultrasound of the kidneys there were diffuse changes in the parenchyma, decreased velocity indices of blood flow in both renal arteries at all levels. Differential diagnosis was carried out with thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, antinuclear form of atypical hemolytic-uremic syndrome, viral and bacterial infections, systemic pathology, antiphospholipid syndrome, and hemoblastosis. The girl didn’t need a renal replacement therapy. When complement-blocking therapy with eculizumab was initiated on vital indications, the signs of the disease were gradually eliminated. The prolonged absence of nephropathy in the child may indicate the diversity of the CD46 gene’s functions and different phenotypic manifestation of its mutations. Analysis of literature sources and detection of CD46 “environment” genes (CYBA, LYST, ARPCIB) by full-exome sequencing suggest ambiguity and polymorphism of phenotypic manifestations of complement-mediated mutation.

Tuberculosis Beyond Borders: A Rare Case of Infratemporal Fossa Infection Leading to Parotid Abscess and Mastoiditis.

Tuberculosis (TB) remains a global health concern, with extrapulmonary TB (EPTB) comprising 15-20% of cases. Diagnosis is challenging due to nonspecific imaging findings, necessitating consideration in high-risk populations. Understanding TB's pathogenesis, including lymphatic and hematogenous spread, is crucial for accurate diagnosis. Radiological assessments play a pivotal role in diagnosis and treatment planning. A 25-year-old male presented with left ear discharge and progressive pre- and infra-auricular swelling. Imaging revealed extensive involvement of the parotid and mastoid regions, posing diagnostic dilemmas. Microbiological confirmation via USG-guided aspiration confirmed mycobacterial TB with Rifampicin resistance, prompting prompt initiation of anti-tubercular therapy. TB extending to the parotid and mastoid regions is rare but warrants consideration in ITF lesions. This case emphasizes the importance of maintaining a high index of suspicion for TB, utilizing advanced imaging modalities, and obtaining microbiological confirmation for precise diagnosis and timely intervention. Further research is needed to optimize diagnostic and therapeutic approaches for atypical ITF infections.

Non-resolving pneumonia with respiratory failure: scratch your neurons too

Finding the etiology for non-resolving or recurrent pneumonia is enough to cause physicians to have sleepless nights. Moreover, if the reason turns out to be the primary presentation of neuromuscular disease, it takes all of us aback. The differential diagnosis should include atypical infections, malignancy, and neuromuscular disorder. We present a case of a 35-year-old female who presented with non-resolving pneumonia with respiratory failure but was later diagnosed with myasthenia gravis.

A Case of Raoultella Ornithinolytica Cholangitis in A Liver Transplant Recipient.

We present the first documented case of Raoultella ornithinolytica bacteraemia in a patient with liver transplantation. R. ornithinolytica is a Gram-negative anaerobic bacterium found in aquatic environments in fish and birds, and is source of nosocomial infection causing pneumonia, enteritis, cholangitis or urinary infections, associated with surgical interventions in a hospital setting. A 44-year-old female presented with a 2-day history of fever, rigors, and headache. Her past medical history was significant for having received three orthotopic liver transplants due to Wilson's disease over a 20-year period. Her physical examination was unremarkable besides stigmata of prior liver transplantation. Blood tests revealed mild elevations in liver function markers and raised inflammatory markers. R. ornithinolytica was eventually isolated from blood cultures. Subsequent magnetic resonance cholangiopancreatography (MRCP) demonstrated new left intrahepatic ductal dilation with heterogeneous peripheral enhancement. The proximal location of the cholangitis explained the lack of abdominal pain or tenderness. The patient was treated with appropriate antibiotic therapy and cultures were negative on day 2. The patient recovered without further intervention. Seldom encountered R. ornithinolytica is uncommonly pathogenic but should be considered in patients receiving immunosuppressants and those with complex surgical anatomy. This is the first case of Raoultella cholangitis in a liver transplant recipient described in the literature.Atypical clinical presentation and atypical infections are common in this patient group.Cholangitis should be suspected in all liver transplant recipients due to immunosuppression.

Concomitant Listeria monocytogenes and Streptococcus equinus brain abscess in an immunocompetent individual: a case report

BackgroundListeria monocytogenes brain abscess is a rare phenomenon that is common in immunocompromised patients. Streptococcus equinus brain abscess has never been reported in the literature to our knowledge. In this case report, we describe a case of brain abscess secondary to Listeria monocytogenes and Streptococcus equinus in an immunocompetent patient with transient low CD4 count.Case presentationA 27-year-old white, male patient, previously healthy, nonalcoholic, and occasional smoker, presented to the emergency department for confusion and headache. The patient was found to have a left parietal abscess, which was drained and the fluid was sent for culture. Culture grew Listeria monocytogenes and Streptococcus equinus. The patient was treated with intravenous ampicillin followed by oral amoxicillin for a total of 6 weeks. The CD4 count was low initially. However, after the resolution of the infection, the CD4 count came back within normal range. Another brain magnetic resonance imaging was done that showed a significantly decreased hyperintensity within the left parietal subcortical white matter at the site of surgery with significantly decreased enhancement and almost total resolution of the previous abscess.ConclusionTransient low CD4 count is a rare phenomenon that exposes patients to unusual and atypical infections. Since low CD4 count is transient, patients treated promptly recover from their illness. Our patient developed a Listeria monocytogenes and Streptococcus equinus brain abscess, which is considered rare and has not been previously described in the literature to our knowledge.

Atypical gouty tophus masquerading as a foreign body granuloma

Subcutaneous nodular lesions in a patient with significantly elevated inflammatory markers always raise the possibility of infectious diagnoses such as atypical infection, pyogenic abscess, mycobacterial infection, and malignancy. Definitive diagnosis requires tissue biopsy and histopathologic examination. The atypical presentation of a foreign body granuloma with concurrent intraoperative findings supports the diagnosis of gouty arthritis.We report a case of a 67-year-old man who presented with an inflammatory nodular lesion on the left elbow that was initially suspected to have an infectious cause. Histopathologic examination of the nodular tissue later revealed that the patient had a foreign body granuloma due to urate crystal deposition. The atypical appearance of the gouty arthritis, the low serum urate level, the negative crystal identification in the synovial fluid, and the markedly elevated inflammatory markers, which did not respond to the previous antibiotic and steroid therapy, raised the suspicion of atypical infection in this case.

Practical considerations in diagnosing inborn errors of immunity according to the Middle East and North Africa guidelines.

The rate of inborn errors of immunity (IEI) in the Middle East and North Africa (MENA) region is generally higher than in other parts of the world. IEI patients in MENA exhibit more severe disease phenotypes. One of the most important reasons for this is delayed diagnosis. In this review, we examine issues pertinent to primary, secondary, and tertiary physicians in diagnosing IEI in children and discuss the key points for pediatricians according to the MENA guideline. Protocols and stepwise approaches designed by a panel of clinical immunologists included in the MENA-IEI registry network can help physicians facilitate the diagnosis of patients with IEI by providing recommendations. These recommendations for diagnostic approaches improve the care of patients within the MENA region and can also be applied to IEI patients in other parts of the world other regions. Physicians in the MENA region should be aware of IEI, obtain a detailed family history, request tests that can be ordered in primary care when IEI is suspected, and refer patients to clinical immunologists without delay. Primary and secondary care physicians should be aware that patients with IEI may present with noninfectious manifestations and increased infection frequency, severity, and atypical infections.