RESUMEN
Key Clinical Message: Partial leukocyte adhesion deficiency type 1 (LAD-1) deficiency is extremely rare condition with milder infectious manifestation and immune system imbalance leads to increased risks of autoinflammatory complications, such as pyoderma gangrenosum, that can be triggered by trauma or pregnancy. In patients with spice-site ITGB2 variants, partial expression can occur due to different ß2 integrin isophorms expression. Abstract: LAD-1, OMIM ID #116920 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene that encodes the CD18 ß2 integrin subunit. According to the CD18 expression, LAD-1 is categorized as severe (<2%), moderate (2%-30%), or mild (>30%). Here, we describe a 22-year-old female, who presented with inflammatory skin disease and oral cavity, as well as respiratory tract infections during the first year of life. LAD-1 was diagnosed at the age of 2 years by low expression of CD18 (1%). Whole-exome sequencing identified homozygous c. 59-10C>A variant in the ITGB2 gene. Despite severe phenotype, the patient survived to adulthood without hematopoietic stem cell transplantation and became pregnant at the age of 20 years, with pregnancy complicated by a pyoderma gangrenosum-like lesion. During her life, CD18 expression increased from 1% to 9%; at 22 years of age, 5% of neutrophils and 9% of lymphocytes were CD18+. All CD18+-lymphocytes were predominantly memory/effector cytotoxic T cells. However, revertant mosaicism was not being established suggesting that CD18 expression variability may be mediated by other mechanisms such as different ß2 integrin isophorms expression.
RESUMEN
Pyoderma gangrenosum (PG) is an uncommon, serious, ulcerating skin disease of uncertain etiology. It manifests as a noninfectious, progressive necrosis of the skin characterized by sterile neutrophilic infiltrates. It seems to be a disorder of the immune system. PG is associated with certain underlying conditions in at least 50% of cases. Therefore, it is important to look carefully for comorbidities in every patient with PG and treat them adequately to improve the prognosis. Here, we demonstrate a 35-year-old man diagnosed with multifocal PG and hemophagocytic lymphohistiocytosis (HLH) with fatal outcome, despite combined, long-term, intensive dermatological and hematological treatment with high doses of steroids, cyclosporin, intravenous immunoglobulins (IVIG), HLH-2004 protocol with intravenously administered etoposide, and anakinra. This case is presented owing to the extremely rare coexistence of PG and HLH and the related diagnostic and therapeutic difficulties. It is also worth underlying that the diagnosis of HLH should perhaps be considered in the presence of a high percentage of double-negative T lymphocytes (DNTs) in flow cytometry, after excluding the diagnosis of lymphoma and leukemia. In this article we have also performed and present the critical literature review of local and systemic options in the management of PG lesions based on a detailed search of the PubMed database.
RESUMEN
In the first part of this article, the anonymous patient diagnosed with leukocyte adhesion deficiency type 1 (LAD-1) and pyoderma gangrenosum (PG) discusses her experience of her medical history and treatment in a foreign country during her pregnancy and the coronavirus disease-19 (COVID-19) pandemic. The patient's dermatologists, immunologist, and diagnostician refer to the epidemiology, genetics, diagnosis, morphologic manifestations, including skin lesions, treatment, and prognosis in LAD-1. The patient's diagnostic and therapeutic process was discussed in the last part of this paper.
