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Rev Alerg Mex. 2025 Sep 30;72(3):94. doi: 10.29262/ram.v72i3.1497.

ABSTRACT

INTRODUCTION: Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults, diagnosed by exclusion in cases of hypogammaglobulinemia without an identifiable cause. Its manifestations range from recurrent infections to autoimmunity and risk of malignancy.

CASE REPORT: A previously healthy 11-year-old female patient was originally from and resides at Rancho El Nogal in Arandas, Jalisco, a community of approximately 250 inhabitants. There was no significant family history; there was no known consanguinity or presence of genetic diseases in the family. Outcome: After trauma to the left leg, she developed osteomyelitis. Upon admission, pancytopenia, enlarged lymph nodes, hepatosplenomegaly, and abscesses with positive cultures for Staphylococcus aureus were detected. An approach to detecting inborn errors of immunity was initiated, revealing decreased immunoglobulin G and A levels. Due to the severe systemic infection, intravenous immunoglobulin was administered at 1 gram/kilogram, and the immunosuppression study was expanded. Abnormalities in the lymphocyte subpopulation were detected, with decreased CD19+ counts: 71 mm³, CD3+ counts: 915 mm³, CD4+ CD45RA+ T cells (naive): 92 mm³, total memory B cells (3%), non-isotype-switched (2.5%), isotype-switched (0.5%), plasmablasts (0.3%), and decreased CD21 counts (9%). The patient was classified as Freiburg 1B common variable immunodeficiency. Monthly intravenous immunoglobulin was started at a dose of 400 milligrams/kilogram. The patient responded favorably to immunoglobulin treatment, with no subsequent serious infections. She remains stable and is being monitored by immunologists.

CONCLUSION: CVID, although more common in adults, can present in children. S. aureus sepsis as an initial manifestation, as in this patients case, should raise concerns about possible underlying immunodeficiencies. This case highlights the importance of suspecting primary immunodeficiencies in patients with severe infections, underscoring the need for early diagnosis and treatment to optimize prognosis.

PMID:41037719 | DOI:10.29262/ram.v72i3.1497

Rev Alerg Mex. 2025 Sep 30;72(3):78. doi: 10.29262/ram.v72i3.1507.

ABSTRACT

OBJECTIVE: This study evaluates the economic burden of hereditary angioedema (HAE) and compares the impact of on-demand treatment versus longterm prophylaxis (LTP) with Lanadelumab, from the perspective of the public health system in Mexico.

METHOD: A systematic literature review and modified Delphi Panel were conducted to understand the resource use of public sector institutions in the diagnosis and treatment of HAE. Costs were obtained from institutional sources such as the IMSS contracting portal and the Diagnosis Related Groups (DRG-2017). The economic burden considered direct medical costs. The results express the annual cost per patient with and without long-term prophylaxis.

RESULTS: With a correct diagnosis, the cost is $5,154.78 MXN (250.20 USD). Without long-term prophylaxis, the annual cost per patient is $3,446,790.56 MXN (167,229.63 USD), with 70% peripheral attacks, 28% abdominal attacks, and 1% laryngeal attacks. Medical expenses are divided into 38% treatment, 36% complications, and 20% hospitalizations. With LTP, the annual cost is $2,641,682.18 MXN (128,221.44 USD), with 8% for attack treatment and 92% for prophylaxis. Prophylactic treatment reduces the economic burden of HAE attacks by 94.2% compared to on-demand treatment and decreases the economic burden by 23% from an institutional perspective.

CONCLUSIONS: HAE represents a high economic burden, affecting hospitalizations and productivity. LTP with Lanadelumab reduces the burden on the Mexican healthcare system.

PMID:41037703 | DOI:10.29262/ram.v72i3.1507

Rev Alerg Mex. 2025 Sep 30;72(3):77. doi: 10.29262/ram.v72i3.1514.

ABSTRACT

INTRODUCTION: Hereditary angioedema (HAE) is a rare disease characterized by episodes of cutaneous and submucosal inflammation. Its global prevalence ranges from 1:50,000 to 1:100,000 individuals and is often underdiagnosed. It is classified into three main types based on C1 inhibitor (C1-INH) levels and functionality. Type 1 is the most common (85% of cases). It is characterized by low plasma concentrations of functional C1-INH as a result of mutations in the SERPING1 gene.

CASE REPORT: We present the case of a 20-year-old male resident of Guadalajara with HAE type 1 diagnosed at age 12 and a history of drug use. He was admitted with edema in the left posterior thoracic region, which progressed to the neck, causing respiratory distress. During ambulance transport, the patient suffered cardiorespiratory arrest, requiring cardiopulmonary resuscitation. He was administered a bradykinin type 2 receptor antagonist and systemic steroid without success, and was admitted to the emergency department under advanced airway management. Laboratory tests and a CT scan revealed no significant findings. Given the persistence of facial edema, a human C1 esterase inhibitor was administered, and the patient was admitted to the intensive care unit for monitoring.

CONCLUSION: Based on laboratory and CT results, substance abuse was suspected as a triggering factor. The literature reports that individuals with cocaine dependence present a persistent proinflammatory state characterized by reduced baseline levels of the anti-inflammatory interleukin IL-10 and a significant increase in the proinflammatory cytokine TNF-α after exposure to stressful stimuli or use. Although the evidence in the medical literature is limited, the use of psychoactive substances could act as a triggering factor for seizures in patients with hereditary angioedema type 1. This case underscores the importance of identifying potential less-studied aggravating factors and suggests the need for a targeted history of psychoactive substance use in patients with HAE. This could be explained by their effects on vasodilation, the release of inflammatory mediators, and increased vascular permeability, mechanisms that promote bradykinin accumulation. Given the potential risk, it is essential to consider drug use in the comprehensive evaluation of precipitating factors in these patients.

PMID:41037702 | DOI:10.29262/ram.v72i3.1514

Rev Alerg Mex. 2025 Sep 30;72(3):73-74. doi: 10.29262/ram.v72i3.1505.

ABSTRACT

METHODS: Patients with HAE type I/II, aged ≥12 years, were included from the EMPOWER and ENABLE studies, who received lanadelumab at the approved dose and had data on the initial attack rate. Subgroups were created based on baseline HAE activity (moderate: ≥1 to <2, high: ≥2 to <, very high: ≥3 attacks/month). The effectiveness of lanadelumab was measured by the reduction in monthly attacks compared to baseline. Safety was assessed by treatment-emergent adverse events (TEAEs).

RESULTS: A total of 123 patients were analyzed, divided into subgroups by baseline activity: moderate (29), high (15), and very high (79). The mean follow-up duration ranged from 577.5 ± 251.7 days (moderate) to 741.1 ± 281.0 days (high). Average HAE attack rates decreased in all three subgroups after lanadelumab initiation: moderate (1.3 ± 0.3 to 0.3 ± 0.4), high (2.0 ± 0.2 to 0.5 ± 0.5), and very high (5.8 ± 3.0 to 0.4 ± 0.7). TEAEs were not severe, mild/moderate, and unrelated to lanadelumab treatment.

CONCLUSION: HAE attack rates decreased after lanadelumab initiation, regardless of baseline activity. Safety was similar across groups; most TEAEs were mild and unrelated to treatment. These data support lanadelumab as a first-line option for long-term prophylaxis.

PMID:41037699 | DOI:10.29262/ram.v72i3.1505

Rev Alerg Mex. 2025 Sep 30;72(3):70. doi: 10.29262/ram.v72i3.1494.

ABSTRACT

BACKGROUND: Job Syndrome is a primary immunodeficiency disorder with an incidence of 1 per million people. It is characterized by elevated IgE levels, eosinophilia, recurrent infections (bacterial and fungal), eczematous dermatitis, musculoskeletal and vascular anomalies. Diagnosis is based on IgE > 1000 IU/ml and eosinophilia. Treatment is multidisciplinary, including bone marrow transplantation, stem cell therapy, and human immunoglobulin.

CASE REPORT: Evolution: We present a 13-year-old male with a history of asthma and atopic dermatitis treated with subcutaneous immunotherapy since 2016. He developed furunculous lesions that progressed to the frontal area, nose, forearms, abdomen, legs, ankles, and feet. Despite treatment with hydroxyzine, mupirocin, tacrolimus, clobetasol, and deflazacort, he showed no improvement. In 2021, he was admitted to the pediatric department, where the diagnosis was confirmed based on Grimbacher criteria. Treatment with human immunoglobulin was initiated, with adequate response. Currently, the patient is in good general condition with persistence of some skin lesions.

CONCLUSIONS: The therapeutic strategy focuses on the prevention and management of infections and symptoms. It is important to identify complications in the early stages of the disease to treat them effectively. This syndrome, although rare, should be considered a serious condition; early identification of this condition is crucial to improve outcomes in patients with similar presentations.

PMID:41037696 | DOI:10.29262/ram.v72i3.1494

MDM Policy Pract. 2025 Sep 29;10(2):23814683251364199. doi: 10.1177/23814683251364199. eCollection 2025 Jul-Dec.

ABSTRACT

Introduction. Limited evidence guides pediatric rheumatologists on when to withdraw biologic therapy in children with juvenile idiopathic arthritis, resulting in wide variation in clinical practice. This study aimed to develop and evaluate a decision support tool (DST) based on expert opinion to support pediatric rheumatologists in making withdrawal decisions. Methods. A literature review, focus groups, interviews, and prior research informed the design of the prototype DST. Evaluation of the DST’s face validity, content validity, acceptance, and feasibility was conducted through user testing interviews and a survey among pediatric rheumatologists from the Netherlands and Canada. Findings were summarized using descriptive and qualitative content analyses. Results. The prototype DST requires input on relevant patient, disease, and treatment characteristics. Its primary output is the predicted likelihood of biologic therapy withdrawal. Pediatric rheumatologists can adjust the importance of characteristics and observe the resulting impact on withdrawal likelihood. Eleven pediatric rheumatologists participated in testing. Key themes identified included the need for 1) clear terminology to ensure consistent interpretation of model inputs, 2) concise instructions on how and when to adjust the relative importance of characteristics, and 3) practice rounds to build trust among pediatric rheumatologists in the DST’s output. Participants found the DST feasible for clinical use, with its main value in explaining decisions to patients and engaging them in the decision-making process. Suggested future improvements include tracking the outcomes of withdrawal decisions and integrating predictive models based on clinical data. Conclusions. The DST developed in this study was well-received. Its main value lies in helping pediatric rheumatologists explain their decisions to patients and parents. The top priority for further development is integrating scientific evidence on successful withdrawal decisions.

HIGHLIGHTS: Decision support tools that provide structure to decisions based on expert opinion can increase transparency and consistency in medical decision making in the absence of clinical evidence.Data from clinical vignette studies that use an experimental design to elicit treatment preferences can be used to predict treatment decision making.A decision support tool to support biologic therapy withdrawal decisions has the most value in explaining the decision to children with nonsystemic juvenile idiopathic arthritis and their parents.

PMID:41036268 | PMC:PMC12480790 | DOI:10.1177/23814683251364199

Front Immunol. 2025 Sep 16;16:1602942. doi: 10.3389/fimmu.2025.1602942. eCollection 2025.

ABSTRACT

Wiskott-Aldrich syndrome (WAS) is an inborn error of immunity caused by loss-of-function mutations in the WAS gene, which encodes WASp, a key regulator of cytoskeletal remodeling. In addition to microthrombocytopenia, affected individuals often present with recurrent infections, eczema, eosinophilia and elevated IgE levels, suggesting a potential pathophysiological overlap with STAT3 hyper-IgE syndrome (HIES). Given these shared features, we investigated the immunogenetic characteristics of three WAS patients and explored the IL-6/STAT3 pathway as a potential underlying mechanism. Flow cytometry revealed absent WASp expression in P1 and P3, while P2 showed reduced level. Genetic analysis identified three hemizygous mutations: A56V substitution within the WH1 domain in P1, and two splice site mutations, c.360 + 1G>T and c.734 + 1G>C, in P2 and P3, respectively. Interestingly, all WAS patients showed impaired STAT3 phosphorylation in T cells following IL-6 stimulation and SOCS3 induction was markedly decreased. These results further suggest a potential link between WASp and STAT3. Considering the interaction of WASp with DOCK8-WIP in lymphocytes and the critical role of DOCK8 in regulating STAT3 phosphorylation following IL-6 stimulation, we analyzed DOCK8 expression in lymphoblastoid cell lines. We demonstrated normal DOCK8 levels suggesting that STAT3 signaling defect is due to the absence of WASp rather than DOCK8 loss. Our results demonstrate the impairment of T cell IL-6/STAT3 pathway in WAS patients which could underlie, in part, the overlapping phenotype with HIES patients.

PMID:41035657 | PMC:PMC12479476 | DOI:10.3389/fimmu.2025.1602942

Intern Med. 2025 Oct 2. doi: 10.2169/internalmedicine.6174-25. Online ahead of print.

ABSTRACT

Signal transducer and activator of transcription-3 (STAT3) gain-of-function (GOF) syndrome predisposes patients to autoimmunity diseases. Yet, nontuberculous mycobacterial (NTM) infections have rarely been described. We herein report a teenage Japanese patient with genetically confirmed STAT3-GOF syndrome who developed Mycobacterium intracellulare disease. Combination antimycobacterial chemotherapy reduced the bacterial burden; however, the refractory NTM infection relapsed after initiation of adjunctive tofacitinib therapy. The present case demonstrates that host-directed therapy must be combined with prolonged antimycobacterial regimens to control drug-resistant NTM in patients with inborn errors of immunity.

PMID:41034003 | DOI:10.2169/internalmedicine.6174-25

J Allergy Clin Immunol. 2025 Sep 29:S0091-6749(25)00983-2. doi: 10.1016/j.jaci.2025.09.019. Online ahead of print.

ABSTRACT

BACKGROUND: Bacterial translocation is a shared phenomenon in common variable immunodeficiency (CVID) and x-linked agammaglobulinemia (XLA). In CVID, bacterial translocation is linked to systemic immune activation and chronic inflammatory manifestations.

OBJECTIVE: To investigate whether the absence of functional Bruton’s tyrosine kinase (BTK) in XLA is associated with protection against systemic inflammation driven by bacterial translocation, and to assess whether BTK inhibition could modulate these inflammatory responses in CVID.

METHODS: Clinical data from the US national registry were analyzed to compare the incidence of inflammatory complications between CVID and XLA. Serum immune profiling was conducted to assess systemic immune activation associated with bacterial translocation in both disorders. In parallel, ex vivo stimulation assays were used to evaluate the effects of BTK inhibition on microbial-translocation-driven inflammatory responses in CVID.

RESULTS: XLA patients, who lack BTK, were significantly protected from the inflammatory complications commonly observed in CVID. Despite comparable levels of bacterial translocation, serum cytokine profiling revealed that XLA patients exhibited markedly reduced immune activation, with lower levels of IFN-γ pathway mediators (IFN-γ, IL-12b, IL-18, CXCL9), pro-inflammatory cytokines (TNF-α, TNF-β, IL-6), chemokines related to host-commensal junctures (CCL19, CCL23, CCL3), and markers of monocyte and T cell activation. XLA and CVID exhibited differential host responses to bacterial translocation stimuli in vivo and ex vivo, with reduced IFN-ɣ, pro-inflammatory cytokines, and monocyte responses in XLA. Translating these findings, we showed that the use of BTK inhibitors (rilzabrutinib, PCI-29732) in inflammatory CVID PBMCs recapitulated the in vivo differences between CVID and XLA, and effectively attenuated pathogenic immune responses to bacterial translocation stimuli.

CONCLUSIONS: These findings identify BTK as a key host modifier mediating the systemic effects of bacterial translocation. Inhibiting BTK activity in CVID may provide a novel therapeutic strategy to mitigate chronic inflammatory complications in this primary antibody deficiency.

PMID:41033468 | DOI:10.1016/j.jaci.2025.09.019

Front Immunol. 2025 Sep 15;16:1653685. doi: 10.3389/fimmu.2025.1653685. eCollection 2025.

ABSTRACT

INTRODUCTION: Congenital immune system defects represent an ever-growing group of diseases characterized by increased susceptibility to infections and association with autoimmune, autoinflammatory, allergic and malignant complications. Here, we provide the first comprehensive report on inborn errors of immunity (IEIs) in Czechia based on the analysis of patient data from the Czech national registry (CzNR) of IEIs.

MATERIAL AND METHODS: The online platform of CzNR of IEIs was established in 2012, compiling data about epidemiology, type of diagnosis, clinical and laboratory parameters, as well as the treatment of patients diagnosed with IEIs since 1981.

RESULTS: The total of 1,443 registered patients includes 697 males (48.3%) and 746 females (51.7%). The median age at diagnosis was 21.0 (0-86) years. The most represented group of patients was those with antibody deficiencies (788 patients; 54.6%). This was followed by complement deficiencies (242; 16.8%), combined immunodeficiencies with syndromic features (250; 17.3%), combined immunodeficiencies (55; 3.8%), congenital defects of phagocyte number, function, or both (31; 2.1%), autoinflammatory disorders (28; 1.9%), immune dysregulation diseases (24; 1.7%), intrinsic and innate immunity defects (21; 1.5%), primary immunodeficiency phenocopies (3; 0.2%), and bone marrow failure disorders (1; 0.1%). Common variable immunodeficiency (504; 34.9%), hereditary angioedema (222; 15.4%), and DiGeorge syndrome (182; 12.6%) were the most frequent diagnoses.

CONCLUSION: In this article, we report the epidemiology of IEIs in the Czech Republic for the first time based on the CzNR of IEIs data. The prevalence of IEIs is approximately 13.2 patients per 100000 inhabitants of the Czech Republic.

PMID:41030454 | PMC:PMC12477120 | DOI:10.3389/fimmu.2025.1653685