一例由ANCA相关血管炎导致的多器官衰竭致命病例：病例报告与文献综述

《Medicine》：A fatal case of ANCA-associated vasculitis resulting in multiple organ failure: Case report and literature review

Poikiloderma with neutropenia（PN）是一种罕见的常染色体隐性遗传免疫缺陷病，以皮肤色素沉着、中性粒细胞减少及反复感染为特征。本文报道了一例7岁叙利亚男孩PN病例，临床确诊因经济原因未行基因检测，治疗以抗生素为主，辅以维生素补充，强调预防措施如年度流感疫苗和严格防晒。案例凸显资源有限地区PN诊断的挑战及多学科管理的重要性。

　　
Poikiloderma with neutropenia (PN) represents a rare genetic disorder characterized by distinctive skin manifestations and compromised immune function. The condition typically emerges in infancy and progresses with age, presenting a combination of poikiloderma (abnormal skin pigmentation and texture), recurrent infections, and chronic neutropenia. This clinical pattern, alongside specific physical features such as short stature, dysmorphic facial features, and nail abnormalities, forms the basis for diagnosis. However, the overlap with other poikilodermas like Rothmund-Thomson syndrome (RTS) and dyskeratosis congenita (DC) complicates accurate identification without genetic confirmation.

The reported case of a 7-year-old Syrian male exemplifies the diagnostic and management challenges encountered in PN. The patient exhibited a triphasic fever pattern, right flank pain, and dysuria, alongside a hyperpigmented rash that developed since infancy. Developmental delays, including delayed speech and social interaction, were noted, alongside physical abnormalities such as sparse scalp hair, abnormal nails, hepatosplenomegaly, and a systolic murmur. These findings collectively suggested PN, particularly given the autosomal recessive inheritance pattern observed in familial cases from Morocco and other regions.

Laboratory evaluations confirmed neutropenia (neutrophils at 49%) and anemia (hemoglobin 5 g/dL), with bone marrow biopsy revealing megaloblastic changes and erythroid maturation arrest. These findings align with the hematological dysfunction seen in PN, often exacerbated by nutritional deficiencies such as vitamin B12. The absence of genetic testing due to financial constraints underscored the reliance on clinical criteria, highlighting a critical gap in healthcare systems where molecular diagnostics are inaccessible.

Management focused on infection control through sequential antibiotic regimens, including piperacillin-tazobactam and colistin, alongside supportive therapies such as vitamin B12 supplementation. Preventive strategies emphasized annual influenza vaccinations and rigorous sun protection to mitigate risks of skin cancer and infection recurrence. The patient’s response to treatment, though not explicitly detailed, aligns with the expectation that early intervention improves outcomes.

A key discussion point revolves around the differential diagnosis between PN, RTS, and DC. While all three involve poikiloderma, critical distinctions exist. RTS is associated with radial ray defects and cataracts, whereas DC presents with specific nail dystrophy and leukoplakia. PN’s hallmark is neutropenia and recurrent bacterial infections, coupled with unique features like ectodermal involvement (sparse hair) and dental caries. The case underscores the necessity for systematic comparison when evaluating overlapping syndromes, particularly in resource-limited settings where genetic testing is unavailable.

The clinical significance of this report lies in its illustration of PN in a low-resource context. The absence of genetic confirmation necessitates a thorough clinical evaluation, including detailed family history and systematic exclusion of other conditions. Notably, the patient’s developmental delays, while not universally reported in PN literature, suggest potential neurocognitive involvement that merits further investigation. This aligns with prior observations of variable neurological manifestations in PN patients, emphasizing the need for comprehensive multidisciplinary care.

Chronic neutropenia in PN significantly elevates infection risk, particularly respiratory and urinary tract pathogens. The case highlighted renal abscess as a severe complication, necessitating prolonged antimicrobial regimens and bone marrow monitoring. Prognosis remains guarded due to infection-related mortality and secondary complications like bronchiectasis. However, early adoption of preventive measures—such as infection surveillance, sun protection, and nutritional supplementation—can mitigate long-term risks.

The case also addresses challenges in diagnosis and management in resource-constrained regions. Limited access to genetic testing forces reliance on clinical criteria, which may be subjective and inconsistent. This underscores the importance of training healthcare professionals in recognizing PN’s phenotypic spectrum, including variations in skin involvement, growth parameters, and immune dysfunction. Multidisciplinary care teams involving dermatologists, hematologists, and geneticists are essential for optimal management.

The reported outcome, while not explicitly detailed, aligns with broader PN management guidelines emphasizing infection prophylaxis and regular monitoring. The patient’s adherence to sun protection and vaccination protocols serves as a model for preventive care in high-risk individuals. However, the lack of long-term follow-up data highlights a limitation in single-case reports, urging larger studies to validate treatment efficacy and outcomes.

This case contributes to the global understanding of PN by documenting its presence in a Middle Eastern population and reinforcing the role of clinical acumen in diagnosis. It also highlights the socioeconomic barriers faced in low-income countries, where the absence of confirmatory testing delays access to targeted therapies. Future research should focus on improving diagnostic frameworks in resource-limited settings and exploring cost-effective interventions to reduce morbidity and mortality.

In summary, this report provides a comprehensive clinical analysis of PN in a Syrian child, emphasizing the interplay between genetic predisposition, environmental factors, and healthcare accessibility. It advocates for heightened clinical suspicion in patients presenting with combined neutropenia, poikiloderma, and recurrent infections, particularly in regions with limited genetic testing infrastructure. The case also reinforces the need for public health initiatives to address nutritional deficiencies and infection prevention strategies in at-risk populations.