Chronic granulomatous disease is an uncommon primary immunodeficiency due to a defect of the killing activity of phagocytes, caused by mutations in any of the genes encoding subunits of the superoxide-generating phagocyte NADPH oxidase system. The incidence is 1 in live births. It can occur from infancy to adulthood, usually in children under 2 years. Bacterial and fungal infections in association with granuloma lesions are the most common manifestations of the disease. Aspergillus species, Staphylococcus aureus, Serratia marcescens, Nocardia species are the most common microorganisms isolated. We describe here a case of a 1-year-old boy with chronic granulomatous disease and invasive pulmonary aspergillosis, Serratia marcescens osteomyelitis and Enterobacter cloacae cervical granuloma.
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The journal's production is being transferred to another publisher. If you want to submit a manuscript to the journal, please email it to bolmedhospinfantmex gmail. The journal receives and publishes original articles in Spanish and in English relating to paediatrics in the following areas: biomedicine, public health, clinical epidemiology, health education and clinical ethics. The journal publishes the following articles types: original research articles, reviews, clinical cases, clinicopathological cases, paediatric themes, public health topics, letters to the editor, and editorial comments by invitation.
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Ocasionalmente afecta el estado general, y origina fiebre, hepatomegalia y esplenomegalia.. Background: Sarcoidosis is a systemic disease of unknown etiology that rarely occurs in children.
It usually affects the lungs; however, it may involve various organs. It occasionally affects the general condition, and causes fever, hepatomegaly and splenomegaly.. Case report: We report the case of a twelve-year-old adolescent with late-onset childhood sarcoidosis which diagnosis was confirmed by lymph node histopathological study.
The patient presented general condition, hypercalcemia, erythema nodosum, severe lung disorders, lymphadenopathy, hepatomegaly and testicular mass. He received treatment with steroids, with excellent clinical response.. Conclusions: We highlight the importance of considering the diagnosis of sarcoidosis in patients with hepatomegaly, lymphadenopathy, diffuse lung damage, erythema nodosum, testicular mass and hypercalcemia, as well as the need for a multidisciplinary approach to assess multiple organ involvement and the early beginning of steroid treatment in order to prevent the progression of the disease..
Sarcoidosis is a chronic systemic disease of unknown etiology and worldwide distribution which is usually diagnosed in adults. Sarcoidosis in childhood is very rare.
Lungs are the most frequently affected organs; however, the disease can involve other organs such as eyes, skin, lymph nodes and joints. Less often it involves the nervous system, heart and urogenital tract, causing nephrolithiasis and a testicular mass; in some cases, fever of unknown origin with splenomegaly and hepatomegaly are observed. The diagnosis of sarcoidosis is made by exclusion of other diseases. Therefore, once there is clinical suspicion, a biopsy of the organs involved shows, as a characteristic histopathological finding, the presence of noncaseating epithelioid granulomas.
The first descriptions of sarcoidosis were made in Europe in the late nineteenth century. In , in England, J. Hutchinson studied a patient with chronic skin lesions, arthritis and chronic renal failure, and named the skin findings papillary psoriasis.
In France, in , E. Besnier also described the skin lesions and named them lupus pernio. In , in Denmark, C. Boeck labeled the skin histological lesions with the term sarkoid because of its similarity with sarcoma. In , in Sweden, N.
The neurologic involvement in sarcoidosis was reported by C. Heerfordt in who described patients with uveo-parotid fever and lesion of cranial nerves. The acute pulmonary form of sarcoidosis accompanied of mediastinal lymphadenopathy and erythema nodosum, arthritis and uveitis was described in Sweden in by S.
For more than years, most of the studies on sarcoidosis have been performed in adults. However, pediatric cases have been reported since The condition was known as Besnier-Boeck-Schaumann disease until when the Sarcoidosis World Congress was carried out in London and the term sarcoidosis was generalized. Nowadays, accordingly to the international consensus established by the American Thoracic Society, the European Respiratory Society and the World Association for Sarcoidosis and Other Granulomatosis, sarcoidosis is considered to be a systemic granulomatous disease of unknown etiology, which usually affects adults, and is very rare in children.
The incidence and severity of sarcoidosis vary in different regions of the world and in different ethnic groups probably due to variations in environmental exposures, the prevalence of HLA alleles and other genetic factors. There are very few epidemiological data on children. The rate of morbidity of childhood sarcoidosis is 0. Regarding mortality from sarcoidosis, during the period the National Center for Health Statistics reported sarcoidosis as a cause of death in 10, of 29,, deaths which represents a rate of 2.
However, mortality in the African-American population was 12 times higher than in Caucasian population. In Mexico, the incidence of sarcoidosis is low, probably due to genetic factors or underreporting of cases.
Therefore, there are no studies on the epidemiology of childhood sarcoidosis since only thirteen cases have been published in the last 20 years, including the case of a teenager with lung disease published by the National Institute of Respiratory Diseases and another report from the National Institute of Pediatrics about two cases of early-onset cutaneous sarcoidosis. Sarcoidosis is a chronic inflammatory disease that results from the action of an environmental agent that triggers an initial immune response of T-helper cells type 1 Th1 and leads to the development of noncaseating granulomas with systemic involvement in genetically susceptible individuals.
According to epidemiological findings of the multicenter ACCESS A Case Control Etiologic Study of Sarcoidosis , some environmental conditions are associated with an increased risk for developing sarcoidosis, generating antigenic stimuli, which act as a trigger of the process. Some of the environmental conditions studied are organic materials ragweed, pine leaves and seeds , inorganic materials silica, beryllium, zirconium, titanium, aluminum and fiberglass and microorganisms Mycobacterium tuberculosis, Propionibacterium acnes, Brucella, Borrelia, Leptospira, Mycoplasma, Leishmania and Schistosoma.
Although an infectious agent has not been conclusively identified by culture or by ribosomal RNA markers in tissue from biopsies , the hypothesis of a microbiological agent is the most accepted because there is clinical and epidemiological evidence of transmissibility of sarcoidosis. This observation comes from transplant patients who have developed the disease after tissue or organ transplantation from donors with sarcoidosis.
Besides, it has been reported the development of sarcoidosis in the transplanted lung of a patient suffering from the disease; moreover, animals implanted with tissue from affected patients develop granulomas. The existence of a predisposing genetic factor explains the higher incidence of the disease in relatives of patients with sarcoidosis, as well as differences in the prevalence and clinical course of the disease in different ethnic groups.
The immune mechanisms that cause sarcoidosis are not completely known but it is assumed that macrophages do not adequately recognize and present antigens to T lymphocytes.
However, patients with sarcoidosis do not have other evident manifestation of a cellular or humoral immunodeficiency. The process begins when the antigen phagocyted by the macrophage and the dendritic cell are presented on the MHC site. These chemokines maintain cell recruitment at sites of granuloma formation by their chemotactic effect.
T-regulatory cells from patients with chronic active sarcoidosis have altered function which leads to the persistence of inflammatory process and progression of granulomas. These proteins reduce the formation of granulomas but, on the other hand, lead to the development of fibrosis due to the activity of some macrophage cytokines, like type1-insulin growth factor IGF-1 , platelet growth factor, IL-4 and IL which generate fibroblast activation and collagen and fibronectin deposition in the extracellular space.
The cause of progression to this fibro-proliferative form is unclear, but it may involve the loss of apoptotic mechanisms, loss of regulatory response, or persistence of an antigen that cannot be recognized or properly processed, which causes fibrous scarring and repair of the affected tissue with chronic and irreversible damage. Vitamin D deficiency has been shown to lead to an increased risk of sarcoidosis, as the antigen presenting cells macrophages, monocytes and dendritic cells have vita-min D receptors.
Furthermore, it has been found that activated macrophages are capable of producing active vitamin D3 calcitriol or 1,dihydroxycholecalciferol and parathyroid hormone related peptide PTHrP , which could contribute to hypercalcemia and hypercalciuria frequently present in this condition. One of the most remarkable findings in sarcoidosis is an immunological paradox. This paradox is characterized by intense cellular immune response in the affected organs in contrast to a situation of peripheral immunological anergy, observed as a lack of response to PPD and other intradermal tests.
Another phenomenon which is also subject of interest and controversy is the formation of granulomas in the skin of patients with sarcoidosis four to six weeks after the application of sarcoid tissue extract in the Kveim-Siltzbachtest used in the past for diagnostic purpose.
The histological finding characteristic of sarcoidosis is the presence of noncaseating epithelioid granulomas diffusely scattered in different tissues that mainly affect lymph nodes.
The granulomas of sarcoidosis have compact appearance with well-defined borders. They may be at different stages of development, ranging from highly cellular granulomas to structures of decreased cellularity with fibrosis or progressive hyalinization; besides, they do not have central necrosis neither foreign bodies, in contrast to granulomas caused by mycobacterial and fungal infections, or infestations by systemic metazoans.
The typical sarcoidosis granuloma has two characteristic zones described below:. The central zone or follicle is a dense cluster of epithelioid cells, accompanied by lymphocytes, macrophages, Langhans multinucleated giant cells, mast cells and fibroblasts. Immunohistochemical staining shows that the central zone of an active granuloma has macrophages in various stages of activation and differentiation. The peripheral zone is formed by a ring of lymphocytes, monocytes and fibroblasts.
In the chronic form of the disease, granulomas may be encapsulated by a fibrous halo or may be replaced by scars of fibrous and hyaline tissue. The clinical presentation of sarcoidosis in children varies as it depends on the extent of the disease and the organs involved. In most cases of childhood sarcoidosis, multiple organs are affected with a diffuse inflammatory reaction that causes systemic symptoms such as fever, fatigue, hyporexia, nausea and weight loss, in addition to the specific signs and symptoms arising from dysfunction of each affected organ.
Early onset sarcoidosis or Blau syndrome: It occurs before age five sporadically or in a familiar cluster. Late onset sarcoidosis: It develops in children older than 5 years and resembles the adult clinical form. Most cases occur in an acute form, with malaise and non-specific respiratory symptoms such as dry cough, dyspnea and airway hyperresponsiveness, but the disease can start insidiously and with minimal symptoms.
The condition is mainly located in the pulmonary interstitium, with enlarged hilar, tracheobronchial and mediastinal lymph nodes. Spirometry and plethysmography show a restrictive pattern, coincident with pulmonary dysfunction, and are useful to assess disease progression and response to treatment.
Sarcoidosis may be stratified in four radiographic stages, which guide the clinician to choose the treatment plan and to make a prognosis. In addition, radiographic imaging allows the follow up of the disease; the probability of remission decreases according to the stage of evolution of the lesions.
This is, while radiographic resolution in the first three stages of the disease is feasible, during stage IV, which is considered the end stage, radiographic lesions are already irreversible 37 Table 1.
The characteristic lesion is uveitis. However, conjunctiva, sclera, crystalline and lacrimal glands may also be affected, resulting in cataract, glaucoma and dr y keratoconjunctivitis.
The most frequent lesion is erythema nodosum, used as a marker of acute sarcoidosis since it usually disappears in weeks. Other skin lesions include subcutaneous nodules, psoriasis like plaques, alopecia, hyper-pigmented lesions and leukocytoclastic vasculitis. When polyarthritis, rash and uveitis occur in children under 5 years, it is recognized as Blau syndrome.
Echocardiographic findings include ventricular dysfunction and decreased ejection fraction of the left ventricle; however, histological evidence of myocardial biopsies requires cardiac catheterization. Exocrine glands are frequently affected. Clinical genitourinary involvement has been reported in 0.
The diagnosis of childhood sarcoidosis is performed with the same criteria established for adults, published by the American Thoracic Society and the European Respiratory Society in Histological evidence of noncaseating granulomas in biopsies obtained from the affected organs.
Exclusion of other pathological processes that may present with a similar clinical or histopathological presentation, especially mycobacterial and fungal infections and other immunological processes. There is no definitive test available to confirm the diagnosis of sarcoidosis.
However, auxiliary studies are:. Kveim-Siltzbach test has been used for sarcoidosis diagnosis since It consists of an intradermal inoculation of a suspension obtained from spleen tissue of patients with sarcoidosis; a skin biopsy should be performed 6 weeks after inoculation in search of granulomas. It is also useful as a marker of disease activity as the enzyme levels descend when patients are in remission. Measurement of soluble receptor of interleukin-2 sIL-2R is a test that has been very useful in evaluating the activity of the sarcoidosis.
We present the case of a twelve-year-old male with no relevant family history, parents and four siblings healthy. He was the product of a first pregnancy, born at term by vaginal delivery without perinatal complications.
Resumen de Enfermedades, Afecciones y Lesiones
Doença granulomatosa crônica_relato_caso1
The journal's production is being transferred to another publisher. If you want to submit a manuscript to the journal, please email it to bolmedhospinfantmex gmail. The journal receives and publishes original articles in Spanish and in English relating to paediatrics in the following areas: biomedicine, public health, clinical epidemiology, health education and clinical ethics. The journal publishes the following articles types: original research articles, reviews, clinical cases, clinicopathological cases, paediatric themes, public health topics, letters to the editor, and editorial comments by invitation. SRJ is a prestige metric based on the idea that not all citations are the same.
Correspondencia a:. Objetivo: Reportar 3 casos de lactantes menores con IDP que se manifestaron como infecciones graves de curso inhabitual. Primary immunodeficiency diseases PID are congenital disorders secondary to an impaired immune response. Infections, autoimmune disorders, atopy, and lymphoproliferative syndromes are commonly associated with this disorder.
Chile ; Genetic variants of chronic gra- nulomatous disease: Prevalence of deficiencies of two cytosolic components of NADPH oxidase system. N Engl J Med ; Montoya CJ, Ayala A.