Pyoderma Gangrenosum with an Underlying Leukocyte Adhesion Deficiency Type 1 (LAD-1) and Pregnancy in the Shade of COVID-19 Epidemic: A Patient and Physician Experience

Opalińska, Aleksandra; Burdacki, Adrian; Kwaśniak, Konrad; Pogoda, Katarzyna; Tabarkiewicz, Jacek; Reich, Adam

doi:10.1007/s13555-021-00507-x

Cited by 6 publications

(7 citation statements)

References 34 publications

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“…As has been reported in similar studies, LAD-I 0 was also the predominant phenotype in our population [ 1 , 3 , 22 , 29 , 30 ]. All LAD-I 0 had severe manifestations early in life, and 65% of the ones following in our clinic lost their lives.…”

Section: Discussionsupporting

confidence: 88%

Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children

Saad,

Alkady,

Eldash

et al. 2024

J Clin Immunol

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Purpose Leukocyte adhesion deficiency (LAD) represents a rare group of inherited inborn errors of immunity (IEI) characterized by bacterial infections, delayed umbilical stump separation, and autoimmunity. This single-center study aimed at describing the clinical, immunological, and molecular characterizations of 34 LAD-I Egyptian pediatric patients. Methods Details of 34 patients’ personal medical history, clinical and laboratory findings were recorded; Genetic material from 28 patients was studied. Mutational analysis was done by Sanger sequencing. Results Omphalitis, skin and soft tissue infections with poorly healing ulcers, delayed falling of the umbilical stump, and recurrent or un-resolving pneumonia were the most common presentations, followed by chronic otitis media, enteropathy, periodontitis; and recurrent oral thrush. Persistent leukocytosis and neutrophilia were reported in all patients, as well as CD18 and CD11b deficiency. CD18 expression was < 2% in around 90% of patients. Sixteen different pathological gene variants were detected in 28 patients who underwent ITGß2 gene sequencing, of those, ten were novel and six were previously reported. Three families received a prenatal diagnosis. Patients were on antimicrobials according to culture’s results whenever available, and on prophylactic Trimethoprim-Sulfamethoxazole 5 mg/kg once daily, with regular clinical follow up. Hematopoietic stem cell transplantation (HSCT) was offered for 4 patients. However due to severity of the disease and delay in diagnosis, 58% of the patients passed away in the first 2 years of life. Conclusion This study highlights the importance of early diagnosis and distribution of ITGß2 gene mutation in Egyptian children. Further molecular studies, however, remain a challenging necessity for better disease characterization in the region.

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Section: Discussionsupporting

confidence: 88%

Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children

Saad,

Alkady,

Eldash

et al. 2024

J Clin Immunol

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“…Laboratory analyses typically show neutrophilia due to the inability of neutrophils to properly adhere to the vasculature 2 . We found 20 patients with LAD and associated PG and PG‐like lesions 8,10–22 . Five patients were diagnosed with PG‐like presentations due to positive bacterial cultures or absence of classic PG histopathologic findings; however, bacterial superinfections are not uncommon in PG ulcers and most patients with PG do not present with classic histologic findings 23,24 .…”

Section: Methodsmentioning

confidence: 92%

What can inherited immunodeficiencies reveal about pyoderma gangrenosum?

Oprea,

Kody,

Shakshouk

et al. 2023

Experimental Dermatology

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Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that is occasionally associated with primary immunodeficiency. Though contributions from dysregulation of the innate immune system, neutrophil dysfunction and genetic predisposition have been postulated, the precise pathogenesis of PG has not yet been elucidated. This article reviews reported cases of coexisting PG and primary immunodeficiency in order to gain insight into the complex pathophysiology of PG. Our findings suggest that variations in genes such as RAG1, ITGB2, IRF2BP2 and NFκB1 might play a role in genetically predisposing patients to develop PG. These studies support the feasibility of the role of somatic gene variation in the pathogenesis of PG which warrants further exploration to guide targeted therapeutics.

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“…Details of dermatological aspects and treatment were published in. 24 Pregnancy resolved with the birth of a full-term baby boy with no health problems. After delivery, the woman continued to receive immunosuppression with glucocorticosteroids with a gradual decrease in dosing to prednisolone 10 mg/day and cyclosporine 100 mg twice daily.…”

Section: Cd18 Expression Leukocyte Adhesion Deficiency Pregnancy Pyod...mentioning

confidence: 99%

“…Cyclosporine and prednisolone dosing was further reduced to 3.8 mg/kg. Details of dermatological aspects and treatment were published in 24 …”

Section: Case Presentationmentioning

confidence: 99%

“…22,23 Here, we report on clinical case of adult female with LAD-1 deficiency and variable partial expression of CD18 β2 integrin subunit. Some dermatological aspects and surgical treatment details were published before, 24 but in current report, we present the full clinical story since childhood to present days, genetic conformation of LAD I diagnosis and study of CD18 expression in different patient's age.…”

Section: Introductionmentioning

confidence: 98%

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Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review

Bondarenko,

Boyarchuk,

Sakovich

et al. 2023

Clinical Case Reports

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Key Clinical MessagePartial 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 β2 integrin isophorms expression.AbstractLAD‐1, OMIM ID #116920 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene that encodes the CD18 β2 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 β2 integrin isophorms expression.

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Pyoderma Gangrenosum with an Underlying Leukocyte Adhesion Deficiency Type 1 (LAD-1) and Pregnancy in the Shade of COVID-19 Epidemic: A Patient and Physician Experience

Cited by 6 publications

References 34 publications

Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children

Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children

What can inherited immunodeficiencies reveal about pyoderma gangrenosum?

Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review

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