Stiff-person syndrome (SPS) is a rare autoimmune neurologic disorder characterized by progressive rigidity and spasms, while common variable immunodeficiency (CVID) features hypogammaglobulinemia and recurrent infections. Their coexistence complicates management by requiring autoimmune suppression without further compromising host defense. A 54-year-old man with CVID, diagnosed based on hypogammaglobulinemia (IgG 386 mg/dL) and recurrent sinopulmonary infections, subsequently developed SPS with progressive truncal and limb stiffness, causing gait impairment and dyspnea. He experienced a severe aspergillus pneumonia, and examination showed finger clubbing and resting hypoxemia. Pulmonary function testing demonstrated moderate airflow obstruction with distal airway involvement. Chest radiography later revealed an elevated left hemidiaphragm, consistent with respiratory muscle dysfunction in SPS. Combined therapy with intravenous immunoglobulin (IVIG) and rituximab was initiated, yielding meaningful improvement in stiffness and a reduction in respiratory infections. After a motor vehicle accident with spinal fusion, the patient reported worsening exertional dyspnea and variable IgG troughs; treatment was transitioned to subcutaneous immunoglobulin (SCIG) 10% with rHuPH20 to maintain steadier IgG levels. This case emphasizes the importance of immunologic evaluation in refractory SPS and demonstrates that combined IVIG and rituximab can provide functional benefit while addressing CVID. Transition to SCIG may stabilize IgG exposure and sustain clinical gains. A timeline of diagnoses and treatments highlights the interplay between autoimmunity and hypogammaglobulinemia and supports a tailored, multidisciplinary strategy.

Common variable immunodeficiency disorder (CVID) is diverse, both in its clinical presentation and in the types of deficiency. It is a primary humoral immunodeficiency disorder characterized by reduced serum levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) or immunoglobulin M (IgM), recurrent sinopulmonary infections, autoimmune disorders, granulomatous diseases, enhanced risk of malignancy, and impaired antibody response despite the adequate number of B cells.[1][2] It is the most frequent symptomatic primary immunodeficiency disorder worldwide.[2][3] Rather than a disease, it is a collection of hypogammaglobulinemia syndromes resulting from various genetic defects (almost all of them are specific molecular defects with as yet an unknown cause),[1] named “variable” because of its heterogeneous clinical manifestations.[4]

Immunodeficiencies in adults are increasingly recognized yet often remain underdiagnosed, leading to significant morbidity from recurrent infections, autoimmunity, and malignancy. Both primary immunodeficiencies (PIDs), now known as inborn errors of immunity (IEI), and secondary immunodeficiencies (SIDs) contribute to immune dysfunction in adults. Although SIDs are more common in adults due to factors like medications, malignancies, metabolic disorders, chronic conditions, and protein-losing conditions, IEI-particularly common variable immunodeficiency (CVID)-can also manifest in adulthood with diverse clinical features. Early recognition is crucial, with key warning signs including recurrent sinopulmonary infections, unexplained autoimmunity, poor vaccine responses, chronic diarrhea, bronchiectasis, and persistent lymphadenopathy. The diagnostic approach should be systematic. It begins with a detailed patient history and status followed by the evaluation of immunoglobulin levels, lymphocyte subsets, vaccine-specific antibody responses, and exclusion of secondary causes. Genetic testing, increasingly accessible, plays an important role in confirming the diagnosis of IEI and guiding prognosis and treatment. Management strategies focus on treating the underlying condition in SIDs. Preventive measures, including antimicrobial prophylaxis, vaccination, and immunoglobulin replacement therapy (IGRT) in patients with significant antibody deficiencies, are essential for reducing infections and complications in high-risk patients. Given the growing recognition of adult-onset immunodeficiency, clinicians should maintain a high index of suspicion and adopt a structured diagnostic and management approach to improve patient outcomes and quality of life.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by impaired motile ciliary function, resulting in defective mucociliary clearance and chronic sinopulmonary disease. Although lower airway manifestations are well known, sinonasal disease is often underrecognized or undertreated outside specialist centers, particularly in adults and in settings without routine Ear-Nose-Throat evaluation.

Hatipoglu immunodeficiency syndrome (HATIS) is an autosomal recessive immunologic disorder, characterized by cytopenias, recurrent infections, and failure to thrive associated with biallelic mutation in DPP9 gene. We report 8-month-old pair of twins born to a nonconsanguineous marriage with similar presentation showing severe anemia and recurrent sino-pulmonary infections requiring multiple hospitalizations and blood transfusions with investigations suggestive of macrocytic anemia unresponsive to B12 supplementation. Immunodeficiency workup showed positive Dihydrorhodamine test suggestive of chronic granulomatous disease and whole exome sequencing displayed DPP9 mutation in both the twins.

Kartagener syndrome, a clinical variant of primary ciliary dyskinesia (PCD), is a rare autosomal recessive genetic disorder caused by defective motility of cilia lining the respiratory tract, fallopian tubes, and middle ear. This results in impaired mucociliary clearance and leads to recurrent upper and lower respiratory tract infections, chronic sinusitis, otitis media, and bronchiectasis. We report a case of a 36-year-old woman with longstanding recurrent sinopulmonary infections, productive cough, hemoptysis, and dyspnea, who was ultimately diagnosed with left lower lobe bronchiectasis and situs inversus totalis. Bronchoscopy with bronchoalveolar lavage grew Pseudomonas aeruginosa. In the absence of advanced confirmatory tests for PCD, such as nasal nitric oxide measurement, saccharin test, high-speed video microscopy, transmission electron microscopy, and genetic analysis, the diagnosis was made on the basis of clinical and radiological findings alone. This case underscores the practical challenges of diagnosing Kartagener syndrome in resource-limited settings with constrained access to advanced diagnostic tools, gold-standard genetic tests, specialized personnel, and comprehensive healthcare infrastructure. In our setting, access was limited to basic hematological and biochemical tests and a conventional chest X-ray. It further examines whether a strong clinico-radiological correlation can be sufficient to guide appropriate treatment and management in such contexts.

Hyper-immunoglobulin E syndrome (HIES) and idiopathic eosinophilia lie on the same spectrum of immunodeficiency disease; therefore, physicians need to consider both possibilities as differential diagnoses for early identification. HIES is a primary immunodeficiency syndrome characterized by markedly elevated total IgE levels along with recurrent eczematous rash, skin infections, sinopulmonary infections, and multiple hospitalizations. Similarly, patients with idiopathic hypereosinophilic syndrome (HES) also present with marked eosinophilia, recurrent sinopulmonary infections, and evidence of organ damage such as eosinophilic myositis. Idiopathic eosinophilia also lacks any identifiable secondary aetiology and evidence of organ damage, with only eosinophilia in bone marrow. Both our cases have similar symptoms, presenting in the busy outpatient department settings that needed thoughtful consideration for the differentials. Awareness among Clinicians about this wide spectrum of differentials with overlapping presentations will facilitate early diagnosis and eventually enable optimal cost-effective treatment for patients.

The int22h1/int22h2-mediated Xq28 duplication syndrome is an X-linked intellectual disability syndrome characterized by variable degrees of cognitive impairment (typically more severe in males), a wide spectrum of neurobehavioral abnormalities, and variable facial dysmorphic features. Affected males also exhibit a peculiar combination of recurrent sinopulmonary infections and atopy, findings that have not been observed in affected females. All males reported to date with the syndrome have moderate-to-severe intellectual disability; in contrast, a minority of heterozygous females have been reported to have mild intellectual disability, while the majority have no discernible health or learning issues and are considered clinically unaffected.

Hyper IgE syndrome (HIES) is a rare primary immunodeficiency that is characterized by elevated serum IgE levels, recurrent sinopulmonary infections, and chronic eczema, among other symptoms. Though reports on patients with HIES exist, they primarily focus on the clinical features, diagnosis, and management of HIES without detailing surgical interventions. Here, we present the surgical management of an extensive cellulitic infection that developed into skin necrosis in an HIES patient with a history of polysubstance abuse. The patient had a diagnosis of Job's syndrome, the autosomal dominant form of HIES. In this case, severe infection resulting from immunodeficiency led to cellulitis and full-thickness tissue loss in the left upper limb. Due to the extent of infection and necrosis, multiple debridements and upper extremity reconstructions were necessary for limb preservation. The 625 cm[2] wound, which involved the left upper extremity and crossed the elbow joint, was managed with initial debridement followed by a period of local wound care to allow for clearance of infection. We then performed reconstruction in a staged fashion with dermal substitute (Integra, Integra LifeSciences Holdings Corporation, Princeton, NJ) placement and split-thickness skin grafting (STSG). In this case, we demonstrate that the extensive soft tissue infections that may be found in HIES patients can be successfully managed with skin grafting and dermal substitutes.