Distribution and clinical features of primary immunodeficiency diseases in Chinese children (2004-2009).

Two hundred and one patients have been diagnosed with primary immunodeficiency diseases (PIDs) in our center from January 2004 to December 2009. The male-to-female ratio was 5.29:1. Spectrums of PIDs were as follows: predominantly antibody deficiency disease was the most common category (94 patients, 48.2%), followed by other well-defined immunodeficiency syndromes (40 patients, 20.5%), combined T and B cell immunodeficiencies (33 patients, 16.9%), congenital defects of phagocyte number and/or function (21 patients, 10.8%), and diseases of immune dysregulation (six patients, 3.1%). Agammaglobulinemia was the most frequent disease type. The median of diagnosis lag was 18.0 months. Pneumonia was the most common manifestation of PID patients. Some manifestations were prone to concentrate in certain diseases. As for therapy, 99 patients (50.8%) received intravenous immunoglobulin replacement therapy; 13 patients received hematopoietic stem cell transplantation and nine of them were still alive. In this study, we sought to describe and analyze the distribution, clinical features, and therapy methods of PIDs among children diagnosed in our country and to compare with reports from other countries and regions.

Congenital sensory neuropathy as a differential diagnosis for phagocytic immunodeficiency.

There are few reports about congenital indifference to pain or Hereditary and Sensory Autonomic Neuropathy (HSAN). Several investigations for pathophysiology of this syndrome have been performed and different classifications about it. In this report we present a case of HSAN type II with general absence of pain and self amputations and leprosy-like damage of extremities which was suspected to be phagocytic immunodeficiency due to past history of repeated ulcer and abscess formation.

Defective priming of the phagocyte oxidative burst in a child with recurrent intracellular infections.

Human phagocytes (polymorphonuclear neutrophils and monocytes) play a critical role in host defense against invading microorganisms. Recent studies reported that circulating phagocytes undergo a final maturation process, in particular in terms of oxidative burst, during extravasation and migration to local sites of inflammation. This process is known as priming. We report here on a nine-year-old boy with successive disseminated infections due to intracellular microorganisms (Mycobacterium bovis, BCG, and Salmonella typhimurium). No T- or B-cell quantitative or qualitative defects were found. Polymorphonuclear neutrophil (PMN) migration and NADPH oxidase in PMNs and monocytes stimulated with various agents at optimal concentrations were normal, ruling out a leukocyte adhesion deficiency syndrome, a Chediak Higashi syndrome, and a chronic granulomatous disease. Nevertheless, the patient's PMNs and monocytes showed defective priming capacity, as measured by H(2)O(2) production after pretreatment with LPS (5 microg/mL for 30 min), TNFalpha (100 units/mL for 30 min), or IL-8 (50 ng/mL for 30 min) in response to bacterial N-formyl peptides (fMLP 10(-6) M for 5 min). In these conditions, H(2)O(2) production of PMNs and monocytes from the patient did not exceed that of the samples treated with fMLP or LPS alone, while the controls strongly produced H(2)O(2). Moreover, monocytes from the patient showed an impaired capacity to kill S. typhimurium in vitro. Such an impairment could be related at least in part to the priming deficiency of phagocyte oxidative burst. This case suggests, for the first time, that in vivo priming processes are critical in host defence against intracellular pathogens.

Clinical and laboratory work-up of patients with neutrophil shortage or dysfunction.

Neutrophils have a crucial function in the defense against bacteria and fungi. Indeed, during chronic, severe neutropenia and in case of severe neutrophil dysfunctions, the patients may suffer recurrent and sometimes life-threatening infections. This article describes the clinical symptoms, the theory behind the antimicrobial systems of neutrophils, the methods to diagnose the various aberrations, and the possibilities for treating these patients. A few of the most common causes of neutropenia and neutrophil dysfunctions are described in detail, including recent genetic information regarding the cause of these diseases.

Abnormal peroxidase-positive granules in "specific granule" deficiency.

"Specific granule" deficiency (SGD) has been previously associated with lactoferrin deficiency. The antimicrobial peptides termed defensins, comprising 30% of normal primary granule proteins, have also been shown to be markedly deficient in SGD. The present study was undertaken to correlate these findings with ultrastructural morphometric analysis and peroxidase cytochemistry. Peroxidase-positive, rim-stained, large, defensin-rich dense granules, previously described as a subpopulation of azurophil or primary granules in normal neutrophils, were markedly decreased in a patient with SGD. Morphometric studies of peroxidase-positive granules indicated an average peroxidase-positive granule area (all profiles) in the patient of 0.019 +/- 0.017 micron 2 (mean +/- SD, n = 941) compared to control values from normal neutrophils of two volunteers of 0.049 +/- 0.033 micron 2 (n = 896) and 0.050 +/- 0.039 micron 2 (n = 873) (P less than 0.001 between patient and control samples). Granule histograms showed a single peak of small peroxidase-positive granules, whereas control samples contained more prominent subpopulations of larger peroxidase-positive granules. The total number of peroxidase-positive granules per 100 micron 2 of cytoplasm in the patient was 255 +/- 124 (mean +/- SD, n = 15 cell profiles), which was similar to control values of 266 +/- 63 and 212 +/- 109. Thus, the defensin deficiency in SGD is associated with a decrease in size rather than number of peroxidase-positive granules; suggesting that defensins contribute to normal peroxidase-positive granule size and that SGD is a more global granule deficiency than originally thought.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal Job's syndrome featuring a vesicular eruption.

A newborn infant who developed a vesicular eruption, clinically indistinguishable from herpetic lesions, eventually developed the classic features of Job's syndrome. The initial ares of involvement included the hands and feet, then the scalp, face, and suprapubic skin. The clear, tense vesicles varied only slightly in size and appeared as isolated, grouped, or confluent lesions on inflamed skin. Many eventually became umbilicated. The more typical eczematous component appeared over the course of the next several months. Although the child initially had an elevated white blood cell count and eosinophilia, his IgE level did not become dramatically elevated until after 1 year of age. Job's syndrome should be considered as part of the differential diagnosis of a vesicular eruption in the newborn.

Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome.

A 29-yr-old woman presenting with granulomatous colitis and a chronic perirectal abscess was found to have localized cryptococcosis associated with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome. Similarity to previous cases of esophageal cryptococcosis and ileocecal histoplasmosis suggests an association between the hyperimmunoglobulinemia E-recurrent infection syndrome and localized fungal infections of the alimentary tract. To our knowledge, this is the first well-documented case of cryptococcosis confined to the colon and perirectal tissues.

Phagocytic defects--monocytes/macrophages.

Mononuclear phagocytes originate from stem cells in the bone marrow which differentiate from monoblasts into promonocytes, then into circulating blood monocytes. Subsequently the monocytes can develop into macrophages and reside in a variety of tissues. Mononuclear phagocytes have cell surface receptors for a variety of substances (e.g., IgG, complement components, fibronectin, and sugars) and are capable of secreting a number of mediators (enzymes, complement components, coagulation components, and monokines). The tissue macrophages adapt to their environment and express unique differentiated functions that are related to various anatomic sites and organs (e.g., Kupffer cells, pulmonary alveolar macrophages, osteoclasts, microglia). Macrophages have the capacity to become "activated" by both specific and nonspecific immunologic stimuli and the "activated" macrophage has enhanced functional capabilities (e.g., tumoricidal, microbicidal, phagocytosis, secretion of mediators). Abnormal monocyte/macrophage function may be acquired or may be due to genetic or developmental disorders. Because of their central role in host defense (in inflammatory responses, in antigen presentation, and in immunoregulatory networks), monocyte/macrophage dysfunction may result in one or more pathophysiologic consequences: defects in monocyte maturation, deficiencies in the clearance of physiologic substrates in lysosomal diseases (e.g., Gaucher's disease, mucopolysaccharidoses, osteopetrosis, metachromatic leukodystrophy), decreased synthesis and secretion of mediators (complement component deficiencies), defects in microbicidal activity (chronic granulomatous disease) and defects which are acquired following infection and during chemotherapy (e.g., acquired immune deficiency syndrome).

The hyperimmunoglobulin E recurrent-infection (Job's) syndrome. A review of the NIH experience and the literature.

The hyperimmunoglobulin E recurrent-infection syndrome (HIE) entails a disorder of recurrent bacterial infections of the skin and sinopulmonary tract commencing in infancy or early childhood in the presence of serum levels of IgE which are at least 10 times normal (greater than 2,000 IU/ml). Variable concomitants of HIE are coarse facies, chronic eczematoid rashes, cold cutaneous abscesses, mild eosinophilia, mucocutaneous candidiasis, and a neutrophil chemotactic defect. The bacteria which commonly infect these patients are Staphylococcus aureus and Haemophilus influenzae although Streptococcus pneumoniae and enteric gram-negative rods are seen in some cases. Other than pneumonias, deep-seated infections are unusual, although osteomyelitis, arthritis, and visceral abscesses are seen. Bacteremia and sepsis are rare. Therapy should involve prolonged intravenous antibiotics and early surgery to treat infections which usually seem deceptively benign. HIE patients' neutrophils display a variable chemotactic defect, and their mononuclear cells variably produce an inhibitor of neutrophil chemotaxis. The production of the inhibitor correlates with the in vitro chemotactic defect. The basis of the propensity for recurrent infections is still speculative, and the further study of this syndrome should add new dimensions to our understanding of host defenses against bacterial invaders.

Chemotaxis: basic aspects of methodology, mechanisms and pathology.

This review is an attempt to discuss the basic conceptual tools that are a prerequisite for any clinical study of chemotactic defects. They include familiarity with definitions of common terms and with the merits and drawbacks of the several possible in vivo and in vitro assay methods. Cellular mechanisms involved in locomotion are complex. They include basic requirements for cell metabolism as well as receptor recognition, attachment to surfaces and contraction of the cytoskeleton of the cell. Of the many chemotactic factors reported, few are well characterized and universally agreed upon. Similarly, with the use of more stringent criteria, a number of clinical defects of chemotaxis have proven transitory or even artifactual.

Disorders of phagocyte function.

An increasing number of phagocytic defects with cutaneous manifestations and signs in humans are being reported. With the increasing availability of phagocyte assays, detection of phagocyte defects will allow us to dissect the component events and more clearly understand the central role of the phagocytic leukocyte in host defenses of the skin.

Necrotizing granulomatous vasculitis (allergic granulomatosis) of the gallbladder.

A case of necrotizing granulomatous vasculitis limited to the gallbladder and manifesting as acute cholecystitis is presented. The different types of vasculitis are discussed and the characteristics of necrotizing granulomatous vasculitis (allergic granulomatosis) are described.

Acute disseminated phycomycosis in a patient with impaired neutrophil granulocyte function.

A 13-year-old girl with no previously known predisposing disease developed phycomycosis involving the left lung, pleura and shoulder, the left side of the neck, the left thigh, the kidneys and the brain. Prolonged amphotericin B therapy resulted in clinical improvement, but the disease was wide-spread when the patient died 5 months after debut of symptoms from a subarachnoid haemorrhage due to fungal destruction of the basilar artery. During hospitalization, a marked reduction in the bactericidal activity of circulating neutrophil granulocytes was repeatedly demonstrated and the endotoxin stimulated nitroblu tetrazolium test was negative. Together with the demonstration of granuloma formation and the accumulation of lipid-laden histiocytes in the spleen, lymph nodes, bone marrow and the thymus, these findings indicate that the patient had a less severe form of chronic granulomatous disease.

[Familial granulomatous disease: histopathological and histogentic data]. / La maladie granulomateuse familiale données histopathologiques et histogénétiques

The lesions seen in chronic familial granulomatosis are variable and seen in varied combinations: granulomas, often disseminated, pseudotuberculous lesions, histiocytes with a high content in lipofuscins seen in the liver, lymph nodes, spleen and lungs in particular. These lesions may be explained at least in part by a congenital defect in leucocytes, which is peculiar to this hereditary disease, and which concernes bactericidal functions.

Canine granulocytopathy syndrome: neutrophil dysfunction in a dog with recurrent infections.

A male Irish Setter dog had a clinical history of recurrent life-threatening bacterial infections, with associated periods of pyrexia and severe neutrophilia. Examination of a mandibular lymph node biopsy made when the patient was 10 weeks old revealed subacute diffuse suppurative lymphadenitis with reticuloendothelial hyperplasia. Circulating leukocytes isolated from the dog when it was 5 months old had a marked bactericidal defect when compared with cells from clinically normal dogs of the same age. The clinical syndrome in the affected patient resembled that observed in the granulocytopathies described in man and other animals.