Extensive perineal ecthyma gangrenosum in leukocyte adhesion deficiency type 1 associated with Staphylococcus hominis bacteremia.

Leukocyte adhesion deficiency (LAD), a disorder of neutrophil function, is characterized by a defect in leukocyte adhesion to the endothelium. Recurrent infections in the skin, soft tissue, gingiva, and lungs due to Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella sp. are common in these patients. Ecthyma gangrenosum (EG) is an ulcer of skin and subcutaneous tissue with a black eschar and surrounding erythematous halo secondary to a bacterial infection. Here, we report an unusual presentation of LAD type-1 with extensive EG of perineum secondary to Staphylococcus hominis bacteremia treated successfully with combination of granulocyte transfusion and diversion colostomy.

Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1.

A patient with leukocyte adhesion deficiency type 1 (LAD1) had severe periodontitis and an intractable, deep, nonhealing sacral wound. We had previously found a dominant interleukin-23-interleukin-17 signature at inflamed sites in humans with LAD1 and in mouse models of the disorder. Blockade of this pathway in mouse models has resulted in resolution of the immunopathologic condition. We treated our patient with ustekinumab, an antibody that binds the p40 subunit of interleukin-23 and interleukin-12 and thereby blocks the activity of these cytokines, inhibiting interleukin-23-dependent production of interleukin-17. After 1 year of therapy, our patient had resolution of his inflammatory lesions without serious infections or adverse reactions. Inhibition of interleukin-23 and interleukin-17 may have a role in the management of LAD1. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Periodontal diseases in children and adolescents: a clinician's perspective part 2.

UNLABELLED: The general dental practitioner and paediatric dentist are in a unique position to identify and distinguish between a seemingly innocuous condition that may be a normal physiological aberration or an early sign of severe destructive periodontal disease. Although severe destructive periodontal conditions are uncommon in children, it is essential that children receive a periodontal screening as part of their regular dental examination. Early diagnosis ensures a high likelihood of a successful therapeutic outcome, primarily by reduction of aetiologic factors, remedial therapy and development of an effective maintenance protocol. This prevents the recurrence and progression of disease and reduces the incidence of tooth loss. In the first article, we discussed the classification, plaque-induced and non plaque-induced gingival diseases, localized and generalized forms of chronic as well as aggressive periodontitis. In this second article, we discuss periodontitis as a manifestation of systemic disease, necrotizing periodontal diseases, periodontal screening and basic periodontal examination, and treatment of periodontal diseases in children and adolescents. CLINICAL RELEVANCE: Incorporation of periodontal screening in regular dental examination by dentists can help in early diagnosis and treatment of periodontal diseases. This could prevent further progression of disease and reduce the frequency of tooth loss.

Leukocyte adhesion deficiency type I--a focus on oral disease in a young child.

This paper presents a case of the moderate form of Leukocyte adhesion deficiency type 1 (LAD-1) in a 4 year-old boy. LAD-1 is a rare, inherited immunodeficiency that affects 1 in 1 million people yearly. Affected patients are susceptible to recurrent bacterial and fungal infections, impaired pus formation and delayed wound healing. In the oral clinical finding, more important is a generalized prepuberal periodontitis that can affect the primary and permanent dentitions. For this reason cooperation between dentists and pediatricians is essential in these patients. Evaluating immune system in these patients included peripheral blood leukocyte counts, measurement of serum immunoglobulin levels, assessment of complement level and function, flow cytometric analysis of lymphocyte subsets, and tests of phagocytic function (nitrobluetetrazolium test (NBT)). In families with known molecular defect, an earlier prenatal diagnosis is possible by chorionic villi biopsy. The most important focus should be to control infections. Treatment includes systemic antibiotics and in many cases bone marrow transplantation.

Primary Immunodeficiencies With Defects in Innate Immunity: Focus on Orofacial Manifestations.

The field of primary immunodeficiencies (PIDs) is rapidly evolving. Indeed, the number of described diseases is constantly increasing thanks to the rapid identification of novel genetic defects by next-generation sequencing. PIDs are now rather referred to as "inborn errors of immunity" due to the association between a wide range of immune dysregulation-related clinical features and the "prototypic" increased infection susceptibility. The phenotypic spectrum of PIDs is therefore very large and includes several orofacial features. However, the latter are often overshadowed by severe systemic manifestations and remain underdiagnosed. Patients with impaired innate immunity are predisposed to a variety of oral manifestations including oral infections (e.g., candidiasis, herpes gingivostomatitis), aphthous ulcers, and severe periodontal diseases. Although less frequently, they can also show orofacial developmental abnormalities. Oral lesions can even represent the main clinical manifestation of some PIDs or be inaugural, being therefore one of the first features indicating the existence of an underlying immune defect. The aim of this review is to describe the orofacial features associated with the different PIDs of innate immunity based on the new 2019 classification from the International Union of Immunological Societies (IUIS) expert committee. This review highlights the important role played by the dentist, in close collaboration with the multidisciplinary medical team, in the management and the diagnostic of these conditions.

Periodontal manifestation of leukocyte adhesion deficiency type I.

BACKGROUND: Leukocyte adhesion deficiency type I (LAD-I) is an autosomal recessive immunodeficiency disorder characterized by defects in the integrin receptors of white blood cells that lead to impaired adhesion and chemotaxis. Affected patients are susceptible to recurrent bacterial and fungal infections, impaired pus formation, delayed wound healing, and periodontitis. METHODS: A case of generalized advanced periodontal destruction of the permanent and deciduous dentition in a young Jordanian girl with a severe phenotype of LAD-I is presented in this report. The medical diagnosis was made based on the characteristic clinical and laboratory findings, in particular the total absence of CD18, CD11b, and CD11c as determined by flow cytometry sorting. RESULTS: Periodontal findings in this patient include the early onset of the disease, which affected the primary teeth and permanent dentitions, the intense redness and inflammation of the gingiva, and the rapid periodontal destruction that seems refractory to conventional non-surgical periodontal therapy. CONCLUSION: This report emphasizes the importance of the differential diagnosis of severe immunodeficiency disorders in children and adolescents and mandates the importance of combined care by medical and dental practitioners to prevent tooth loss and control oral infection.

Root surface characteristics of children teeth with periodontal diseases.

The present study examined the root surfaces of teeth from children with or without periodontal diseases and with or without systemic diseases. Light microscopy revealed that when compared to control teeth: teeth with chronic periodontitis had similar radicular histology; teeth from children with leukocyte adhesion deficiency, Down syndrome and aggressive periodontitis had narrower cementum areas; teeth from children with hypophosphatasia showed cementum aplasia. Cementum anomalies may facilitate the establishment and progress of periodontitis in children.

Dental implants in a patient with suspected leucocyte adhesion deficiency.

Aggressive periodontitis and premature tooth loss in leucocyte adhesion deficiency (LAD) have adverse functional and psychological consequences on affected individuals. Dental implant rehabilitation might become necessary to overcome the functional and psychological adverse effects of LAD periodontitis, especially in patients with milder forms who are expected to have a relatively normal life expectancy. Outcome of dental implants in patients with LAD has not been previously reported; we describe the dental rehabilitation of a 24-year-old man with clinical features of LAD using endosseous dental implants.

Leukocyte adhesion defect-I: rare primary immune deficiency.

Leukocyte adhesion defect I is a rare disorder (1:1,000,000) caused by diminished expression of CD-18 ß2 integrins on leukocytes leading to abnormal adhesion, migration, and chemotaxis. Clinical manifestations include delayed separation of umbilical cord, omphalitis, recurrent severe infections, impaired wound healing, persistent oral ulcers, and severe periodontitis in primary and permanent dentition. A 5-year-old girl, second-born child to parents with consanguinity, presented with pain and mobility of lower teeth. There was history of recurrent infections and multiple hospital admissions with CD18 level-3% and frame shift mutation in ITGB2, on 21q22.3. There were scars on hands and feet. Oral examination revealed multiple missing teeth and periodontitis in primary dentition. Oral prophylaxis and palliative treatments were performed with periodic follow-ups. Interdisciplinary care is ubiquitous for patients with immune deficiencies. Early consultation with pediatric dentists and exploration of medical history is essential for diagnosis and treatment of rare diseases.

Leukocyte adhesion deficiency in a child with severe oral involvement.

Leukocyte adhesion deficiency is a rare inherited defect of phagocytic function resulting from a lack of leukocyte cell surface expression of beta2 integrin molecules (CD11 and CD18) that are essential for leukocyte adhesion to endothelial cells and chemotaxis. A small number of patients with leukocyte adhesion deficiency-1 have a milder defect, with residual expression of CD18. These patients tend to survive beyond infancy; they manifest progressive severe periodontitis, alveolar bone loss, periodontal pocket formation, and partial or total premature loss of the primary and permanent dentitions. We report on a 13-year-old boy with moderate leukocyte adhesion deficiency-1 and severe prepubertal periodontitis. This case illustrates the need for the dentist to work closely with the pediatrician in the prevention of premature tooth loss and control of oral infection in these patients.

Radiographic and immunohistochemical analysis of leukocyte adhesion deficiency in Holstein heifers.

Radiographic and immunohistochemical analyses were performed in two Holstein heifers with leukocyte adhesion deficiency (BLAD). Severe bone resorption, osteolysis and severe progressive periodontitis in submandibula due to dysfunction of leukocytes in heifers affected with BLAD were demonstrated by radiographic examination. Immunohistochemical analysis of lymph nodes using anti-CD18 monoclonal antibody demonstrated that CD18-positive cells were not found on those from a heifer affected with BLAD, whereas CD18-positive cells were clearly present in lymph nodes from a clinically normal heifer. These characteristic findings support the importance of adherence-dependent leukocyte functions in host defense.

Bovine leukocyte adhesion deficiency--clinical course and laboratory findings in eight affected animals.

The clinical course of Bovine Leukocyte Adhesion Deficiency (BLAD) in eight Holstein Friesian cattle is described. Affected animals were presented with a history of poor thriving and recurrent bacterial infections. Five of these animals had to be killed because of severe respiratory disease shortly after admittance. Three affected animals survived calfhood only as a result of frequent antibacterial treatments. At one year of age, failure to thrive and stunted growth were still evident, but infections requiring antibiotic treatments occurred only sporadically. Clinical manifestations of BLAD were found in the digestive system (gingivitis, periodontitis, alveolar periostitis, diarrhoea), the respiratory system and the skin (impaired wound healing, chronic dermatitis). A leukocytosis based on a mature neutrophilia, which persisted during infection-free periods, was observed in all animals. Granulocytes were substantially deficient of beta 2-integrin expression on their membranes. Anaemia, which was noted in four animals, may be related to the Anaemia of Inflammatory Disease Complex (AID). The serum total protein content increased with time and was associated with elevated gamma-globulin levels. We suggest that, at a certain age, animals affected with BLAD are able to cope with environmental agents due to compensatory mechanisms of the immune system.

Aggressive periodontitis of the primary dentition associated with idiopathic immune deficiency: case report and treatment considerations.

The present case, of a child with an idiopathic immune deficiency and aggressive periodontitis in the primary dentition, serves as an example for the treatment considerations in these cases. Extraction of all the primary teeth proved to be the most adequate treatment. It allowed the child to eat properly and prevented unwanted infections that could endanger the life of the child. The newly erupted permanent teeth have been subjected to careful oral hygiene, clorhexidine topical applications, and have mild gingival inflammation and no attachment loss.

Etiology of leukocyte adhesion deficiency-associated periodontitis revisited: not a raging infection but a raging inflammatory response.

In leukocyte adhesion deficiency type I, neutrophils fail to adhere to blood vessel walls and thus cannot transmigrate to peripheral tissues. Leukocyte adhesion deficiency type I patients invariably experience an aggressive form of generalized periodontitis, which has been historically attributed to defective neutrophil surveillance of the periodontal infection. This time-honored notion has now been challenged by a recent study, which showed that the underlying etiology involves a dysregulated host response that leads to overexpression of the proinflammatory and bone-resorptive cytokine IL-17.

Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss.

Leukocyte adhesion deficiency type I (LAD-I), a disease syndrome associated with frequent microbial infections, is caused by mutations on the CD18 subunit of ß2 integrins. LAD-I is invariably associated with severe periodontal bone loss, which historically has been attributed to the lack of neutrophil surveillance of the periodontal infection. We provide an alternative mechanism by showing that the cytokine interleukin-17 (IL-17) plays a major role in the oral pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients or in LFA-1 (CD11a/CD18)-deficient mice--which exhibit the LAD-I periodontal phenotype--was associated with excessive production of predominantly T cell-derived IL-17 in the periodontal tissue, although innate lymphoid cells also contributed to pathological IL-17 elevation in the LFA-1-deficient mice. Local treatment with antibodies to IL-17 or IL-23 in LFA-1-deficient mice not only blocked inflammatory periodontal bone loss but also caused a reduction in the total bacterial burden, suggesting that the IL-17-driven pathogenesis of LAD-I periodontitis leads to dysbiosis. Therefore, our findings support an IL-17-targeted therapy for periodontitis in LAD-I patients.

Leukocyte adhesion deficiency: a case report and review.

Leukocyte adhesion deficiency (LAD) is a rare inherited primary immunodeficiency disorder characterized by the presence of a defect of phagocytic function resulting from a lack of leukocyte cell surface expression of ß2 integrin molecules (CD11 and CD18) that are essential for leukocyte adhesion to endothelial cells and chemotaxis. A small number of patients with LAD-1 have a milder defect, with residual expression of CD18. These patients tend to survive beyond infancy; they manifest progressive severe periodontitis, leading to partial or total premature loss of the primary and permanent dentitions. Close cooperation with pediatricians and immunologists is often the key to successful management of pediatric patients with LAD. The purpose of this report was to present the case of a 5-year-old boy with moderate leukocyte adhesion deficiency-1 and severe periodontitis, cellulitis and illustrate the need for periodic oral checkups to avoid the progression of oral diseases and prevent premature tooth loss.

Periodontal manifestation of leukocyte adhesion deficiency type I.

Progressive periodontal disease in leukocyte adhesion deficiency children may lead to severe systemic infections and even death. A five-year-old Iranian male child with leukocyte adhesion deficiency I was first seen in December 2005 at the Pediatric Dentistry Department of Shahid Beheshti Medical University and diagnosed with periodontitis as a manifestation of systemic disease. The treatment approach was based on assessing plaque index, oral prophylaxis, periodic supra and subgingival scaling, in addition to strict oral hygiene instruction with a chlorhexidine prescription and restoration of decayed teeth. The patient attended two dental visits at a one month interval. At the second session, an improvement was seen in the plaque index. Gingival inflammation and bleeding were decreased. Unfortunately he did not regularly attend treatment sessions and at the following examination, progression of periodontitis and bone destruction occurred. The present case emphasizes the need for cooperation between medical and dental professionals, parents and the pediatric patient in order to achieve treatment goals in controlling oral infection in these patients.

Osteomyelitis in leukocyte adhesion deficiency type 1 syndrome.

Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old girl diagnosed LAD-I at the age of 7 years was brought to the Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, because of a draining plaque on the left leg for 2.5 years. She had recurrent skin infections and had been treated with repeated courses of different antibiotic combinations, with temporary responses, since 5 years of age. Examination revealed a 7 x 8 cm minimally erythematous hyperpigmented plaque with multiple draining sinuses on the left leg. Tissue culture yielded Pseudomonas aeruginosa. Flow cytometry showed CD18 (18.79%), CD11a (51.59%), CD11b (18.61%) and CD11c(10.60%). A plain radiography of the left leg revealed osteomyelitis. It is highly suggested that patients diagnosed mild to moderate LAD-1 with recurrent skin infection and simultaneous weak response to conventional therapy undergo (BMT) marrow transplant to prohibit subsequent life-threatening complications.