Skin and soft tissue infections

Primary skin infections (ie, pyodermas) typically are initiated by some breach in the epidermis, resulting in infection by organisms, such as Streptococcus pyogenes and Staphylococcus aureus, that normally colonize the skin. Host-associated factors, such as immunosuppression, vasculopathy, neuropathy, or decreased lymphatic drainage, may predispose to skin infection. The clinical syndromes associated with skin infections are often characteristic and are defined most simplistically by anatomic distribution. Although often mild and self-limited, skin infections can be more aggressive and involve deeper structures, including fascia and muscle. This article discusses skin and soft tissue infections, including impetigo, hair follicle-associated infections (ie, folliculitis, furuncles, and carbuncles) erysipelas, cellulitis, necrotizing fasciitis, pyomyositis, septic bursitis, and tenosynovitis.     

Infektionen mit nichttuberkul?sen Mykobakterien bei Patienten mit Immundefekten

Infections caused by nontuberculous mycobacteria (NTM) cause a variety of clinical pictures, like nodular or cavitary lung infiltrations, lymphadenitis or lesions of the skin and soft tissue. In patients with innate or acquired immune deficiencies, an increase of disseminated but also local, atypical disease manifestations is observed. Detailed knowledge about underlying immune defects and the current immune status of patients with suspected NTM infections is indispensable to verify the detection of NTM in clinical specimens which does not necessarily account for a direct disease association. Differences in the growth kinetics of bacteria from the M. avium complex (MAC) which primarily cause lung diseases in contrast to the rapidly growing M. fortuitum and M. chelonae (RGM) involved in skin and soft tissue infections have to be considered in the diagnostics of NTM infections. Emergence of treatment strategies including biologicals in chronic inflammatory diseases resulted in an increase of local and disseminated NTM infections in the past. The duration of NTM treatment may be prolonged in patients with underlying immune deficiencies and disseminated infections. NTM prophylaxis should be discussed in HIV/AIDS patients with severe immune deficiency (CD4 ?<?50/??l) starting with antiretroviral therapy (cART) as NTM infections presenting as lymphadenitis are frequently observed in patients with immune reconstitution inflammatory syndrome (IRIS).     

Partial deficiency of cell-mediated immunity in a child with chronic mucocutaneous candidiasis. Intercurrent meningeal and pulmonary cryptococcosis]

The authors report a new case of partial immune deficiency of cellular immunity, associated with chronic mucocutaneous candidiasis in a 12 Years-old boy. The disease began very early during the first few weeks of life, with thrush in the mouth. This candidiasis then evolved intermittently and was still present. Numerous cutaneous, pulmonary and ear infections occured throughout this child's life. This morbid association led to a search for an immune deficiency. Humoral immunity was normal. Abnormalities of cellular immunity were as follows: apart from candidine skin anergy, there was a deficiency in the factor which inhibits leukocyte migration, secretion of a factor favouring this migration (MEF). It was also noted the presence of the patient's serum, of a factor inhibiting lymphocyte transformation in the presence of candidine. In spite of treatment with intravenous route, amphotericin B, followed by transfer factor, the oral candidiasis persisted together with the skin anergy to candidine. On the other hand, the serum inhibitory factor disappeared. Pulmonary cryptococcosis probably favoured by corticosteroid treatment, developed on this background of immune deficiency; as usual it spread to the meninges. Treatment associating intraveinous amphotericin B and 5 fluorocytosine oral and later intravenous, total duration 6 months, grave a recovery maintained on a 8 months follow up.     

Parasitoses in immune deficiences

The congenital or acquired cause the state of immune deficiency. To acquired factors belong immunosuppressive therapy after grafting and in systemic diseases as infections with HIV. There is a number of parasitic organisms, mainly protozoa, which preferentially settle in immunocompromised persons. The opportunistic parasites are present in the nearest environment. Some of them were newly recognized as human invaders. The state of immune deficiency may reactivate latent infections, that occurs with Toxoplasma gondii infection. Some parasitic infections which are benign and self- resolving, when affecting immunocompetent hosts, become fulminant or disseminated and very often life - threatening in immunosuppressed individuals.     

Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gammac cytokine receptor subunit or JAK-3 deficiency

Haemopoietic stem-cell transplantation is a life-saving treatment for severe combined immune deficiency. However, there has been little long-term follow-up of this treatment. There is evidence for the persistance of partial immunodeficiency associated with significant infections, including severe human papillomavirus (HPV) disease. We did a retrospective analysis of severe HPV disease in a group of 41 patients with severe combined immune deficiency from one centre who were alive 10 years or longer after haemopoietic stem-cell transplantation. Nine of the 41 patients had extensive chronic HPV disease limited to the skin, with a median onset at 8 years after transplantation. Four had lesions typical of epidermodysplasia verruciformis, a rare genodermatosis. Transplant characteristics, immune status, and chimerism of these nine patients did not differ significantly from those of the other patients. The nine patients with HPV disease had severe combined immune deficiency associated with either common gammac receptor cytokine subunit or Janus kinase-3 (JAK-3) deficiency. By contrast, patients with other forms of severe combined immune deficiency did not have any signs of HPV disease. That genetic causes are the only predisposing factor to be identified for severe combined immune deficiency, suggests that natural-killer cells or gammac/JAK-3-dependent signalling in keratinocytes could have a role in anti-HPV immunity.     

Asthma and allergic rhinitis in a patient with BTK deficiency

BTK deficiency is a primary immunodeficiency disease characterized by the absence of circulating B cells and agammaglobulinemia. While recurrent bacterial infections are the most common manifestations, symptoms of allergy and asthma are rare. We present the case of a 7-year-old boy who presented with asthma symptoms, allergic rhinitis, and severe papular urticaria. He had a positive skin prick test to aeroallergens and food allergens. However, further laboratory tests revealed a low number of B cells and decreased serum levels of all immunoglobulin isotypes. Molecular analysis revealed a mutation in the BTK gene. Although patients with BTK deficiency seem to be protected from atopy, our patient had allergic symptoms suggesting a bias toward a type 2 helper T cell pattern in this case. Primary antibody deficiency should be considered in the differential diagnosis of pediatric allergy and asthma when respiratory infection persists despite appropriate treatment.     

Small Intestinal Lymphoma in Three Patients with Acquired Immune Deficiency Syndrome

Three cases of small bowel lymphoma in young homosexual men are presented. All three had acquired immune deficiency syndrome as demonstrated by demography, sexual history, cachexia, opportunistic infections by Cytomegalovirus, Pneumocystis carinii, atypical Mycobacterium, Candida, and/or evidence of immune deficiency, such as skin test anergy, lymphopenia, inversion of T-helper/T-suppressor ratio, and diminished lymphocyte response to either phytohemmaglutinin or pokeweed mitogen. All had peripheral and/or abdominal lymphadenopathy, and gastrointestinal symptoms, e.g., diarrhea, spasms, constipation, and oral candidiasis. The diagnosis of lymphoma was made at laparotomy in all cases. All three had complete removal of localized tumor (stage Ie or IIe), yet died within 6 months of surgery and/or chemotherapy. Thus gastrointestinal complaints may not always be related to "gay bowel" syndrome, or other infectious diseases in patients with acquired immune deficiency syndrome. Small intestinal lymphoma should be added to the list of neoplasms to which this group is susceptible.     

Hematologic complications of primary immune deficiencies

Primary immune deficiencies have an estimated overall incidence of 1 in 10,000 individuals. These disorders are diverse, depending on the specific immune functions involved, and lead to chronic or recurrent infections, inflammatory conditions, and a variety of autoimmune diseases. The most common autoimmune disorder is immune thrombocytopenic purpura (ITP), followed by autoimmune hemolytic anemia (AHA). While cytopenias are common in all the congenital immune diseases, they are particularly common in the antibody defects, common variable immunodeficiency and selective immunoglobulin A deficiency. In common variable immunodeficiency, ITP occurred in 7.6% of the patients and AHA in 4.8%. Treatment options include corticosteroids, intravenous immunoglobulin (i.v.Ig), anti-D, and splenectomy. Although the association between cytopenias and congenital immune deficiency is unclear, defects in T-cell regulation, cytokine defects, abnormal apoptosis, and abnormal production of immunoglobulins with autoimmune features are potential mechanisms.     

Selective antibody immune deficiency in a patient with Smith–Lemli–Opitz syndrome

Summary Smith–Lemli–Opitz syndrome is a rare autosomal recessive disorder characterized by multiple congenital anomalies and various degrees of cognitive deficits. This condition results from a deficiency of 7-dehydrocholesterol reductase, a critical step in cholesterol biosynthesis. Children with Smith–Lemli–Opitz syndrome have frequent infections, particularly of the respiratory tract. Immunodeficiency, however, is not recognized as a part of this metabolic condition. Frequent infections are usually attributed to a decreased patient mobility and reduced respiratory effort secondary to muscular hypotonia and mental retardation, which are often present in affected individuals. We describe a patient with Smith–Lemli–Opitz syndrome and recurrent respiratory infections who was found to have a selective antibody deficiency. The immunological diagnosis was based on an absent immune response to Pneumovax. She also had no immunological response to hepatitis B vaccine and was unable to break down red cells with isoagglutinin B. Therapy with intravenous IgG (IVIG) was initiated. Infections were less severe, although they still occurred in a high frequency after initiation of the IVIG therapy. This finding prompts the need for a higher index of suspicion for an underlying immune deficiency in patients with Smith–Lemli–Opitz syndrome who present with recurrent and chronic infections. Early recognition and appropriate therapeutic interventions may decrease the severity of infections, prevent potentially fatal infections, and eventually improve the quality of life in these patients.     

Granzyme B contributes to extracellular matrix remodeling and skin aging in apolipoprotein E knockout mice

Apolipoprotein E knockout (apoE-KO) mice have been utilized for decades as a model of atherosclerosis. However, in addition to atherosclerosis, apoE-KO mice develop extensive cutaneous xanthomatosis, accelerated skin aging and frailty when fed a high fat diet. Granzyme B (GrB) is a pro-apoptotic serine protease that has recently been shown to exhibit extracellular proteolytic activity in certain pathologies. In the present study, the role of GrB in skin aging and pathology was assessed using the apoE-KO model of skin aging. Male C57BL/6 wild type and apoE-KO mice were grown for 0, 5, 15 or 30 weeks on either a high fat (21.2% fat, 0.2% cholesterol) or regular chow diet (7% fat). ApoE/GrB double knockout (DKO) mice were also generated and assessed after being fed either diet for 30 weeks. Skin was removed from the mid to lower back and examined for age-related changes such as hair loss, skin thinning and collagen remodeling and disorganization. ApoE-KO mice exhibited signs of frailty, hair graying, hair loss, skin thinning, loss of collagen density and increased skin pathologies featuring collagen remodeling and reduced decorin compared to wild type controls. These phenotypes occurred earlier and were more severe when fed a high fat diet. In addition, we also observed increased GrB expression in proximity to areas of decorin degradation and reduced collagen density in the skin of apoE-KO mice. DKO mice exhibited protection against skin thinning, ECM degradation and loss of dermal collagen density. In summary, our results provide novel insights into the effects of a high fat diet and apoE deficiency on skin aging and pathology and suggest a role for GrB in age-related skin thinning and frailty.     

Selective immunoglobulin M deficiency in an adult with Streptococcus pneumoniae sepsis and invasive aspergillosis.

Primary selective immunoglobulin (Ig) M deficiency usually presents early in life with recurrent or severe infections caused by encapsulated and gram-negative organisms. Primary selective IgM deficiency in adults is rare and is usually associated with autoimmune diseases or malignant neoplasm. We performed an extensive immunological analysis of innate and adaptive immunity in an adult patient with possible primary selective IgM deficiency who presented with life-threatening Streptococcus pneumoniae septic shock and invasive Aspergillus fumigatus infection. The patient had no evidence of autoimmune disease or malignant neoplasm. Serum IgG, IgA, and IgE were normal; however, serum IgM levels and specific antibody titers against all 14 pneumococcal polysaccharide serotypes were consistently low. Complement CH50, C3, C4, and neutrophil phagocytosis and oxidative burst were normal. Toll-like receptor expression on monocytes was also normal. Therefore, adult patients with serious life-threatening and unusual infections should be investigated for possible selective primary IgM deficiency.     

Immune deficiency: office evaluation and treatment.

Congenital deficiencies of the immune system occur in children or adults and can cause severe or recurrent infections. The overall incidence of these immunodeficiency diseases is estimated at approximately 1 in 10,000, excluding selective immunoglobulin A deficiency, but this estimation is based on population studies, not hospital or clinic populations. The majority of immune defects involve antibody production; these immune deficiencies are found more often in adults than infants and children. In an allergy practice, recurrent infections are common, and determining if an immune defect is likely to be present can be problematic. Some guidelines concerning the clinical presentation and laboratory evaluation and treatment options can aid the practicing clinician.     

A cluster of male pseudohermaphrodites with 5α-reductase deficiency in Papua New Guinea

We report a cluster of male pseudohermaphrodites from the Simbari Anga linguistic group in the Eastern Highlands of Papua New Guinea. These subjects are born with a rudimentary clitoral-like penis and pseudovaginal perineoscrotal hypospadias. At puberty, the penis enlarges with concurrent growth of pubic and axillary hair and significant muscular development. There is significant facial hair, but it is less than that of their normal male siblings or other male relatives. Plasma collected from four adult subjects revealed elevated plasma testosterone levels, low to low normal dihydrotestosterone levels, and elevated testosterone/dihydrotestosterone ratios. All subjects had high urinary aetiocholanolone/androsterone ratios, and C19 and C21 5 beta/5 alpha metabolite ratios. Decreased 5 alpha-reductase activity was demonstrated in fibroblasts cultured from genital skin. The data indicate a phenotypic and biochemical profile similar to patients studied in the Dominican Republic, except for a greater abundance of facial and body hair. The phenotypic variability, as pertains to facial and body hair, may be related to differences in familial expression, as well as the degree of enzyme deficiency. Infants, thought to be females at birth, were reared as girls until puberty in a society practising one of the strictest gender segregations known. At puberty, these 'girls' were discovered to be boys, and a switch of gender roles was instituted. Recently, however, some Muniri, Dunkwi and northern Simbari hamlets recognize these individuals as male in infancy and rear them as boys, calling them 'kwalatmala' to distinguish them from normal males, accepting them as an intersex destined to occupy male adult roles.     

Activated PI3K-delta syndrome in an Egyptian pediatric cohort with primary immune deficiency

BackgroundActivated Phospho-Inositide 3 (PI3) Kinases Delta syndrome (APDS) can underlie primary immune deficiency. The prevalence and phenotypic characterization of these patients are not well described in Egypt.ObjectivesTo describe patients with APDS in hospitalized children with recurrent respiratory tract infections with suspected primary immune deficiency.Methods79 patients were included in the study. E1021K and E525K mutations of PI3K δ chain gene were screened by Sanger sequencing technique.Resultsone patient was heterozygous to E1021K mutation; a female child was diagnosed clinically as Combined Immune Deficiency with CD4 and B lymphopenia and markedly deficient IgG and increased IgM. The E525K mutation was not detected in our cohort.ConclusionsScreening for APDS in patients with recurrent respiratory tract infections with undefined antibody deficiency or combined immune deficiency with or without bronchiectasis is required. These patients need great attention to benefit from the available treatment. Further studies on the Egyptian population are recommended to increase the knowledge about the prevalence and phenotypic characterization of this disease in Egypt.     

Complement factor I deficiency associated with recurrent infections, vasculitis and immune complex glomerulonephritis

Here we report complement factor I deficiency in an 11-y-old girl from a consanguineous Turkish family, who presented with recurrent pyogenic infections, vasculitic eruptions and immune complex glomerulonephritis. A moderately low C3 level together with the clinical picture suggested a deficiency affecting regulation of complement activation. Analysis of haemolytic activity revealed absence of alternative pathway activity and subsequent analysis showed no detectable factor I (<2%) together with a low level of factor B and a moderately low level of factor H, indicating consumption secondary to the factor I deficiency. Factor I inhibits complement activation beyond C3 by cleavage of C3b in the presence of cofactors. Complement factor I deficiency is frequently associated with recurrent pyogenic infections mainly affecting the upper and lower respiratory tract, or presenting as meningitis or septicaemia, while rheumatic disorders have not been a prominent feature. The patient's sister also suffered from recurrent pyogenic infections and had a low C3 level clearly suggesting the same deficiency.     

Clinicoetiologic investigations on superficial mycoses of Warangal (A.P) India

ObjectiveTo study the clinical manifestations and etiological agents of superficial mycosis and to investigate their relationship in superficial mycosis occurring in Warangal, A.P. India.MethodsThe present study was conducted on 400 clinically diagnosed patients with dermatophytoses. Three different types of samples viz. skin scrapings, hair samples and nail clippings were collected for examinations. The samples were processed for microscopic examination, histological study and culturing of etiological agent. The incidence of various dermatophytic species in relation to clinical types was recorded.ResultsAmong different clinical types, tinea corporis was most common. The most frequently isolated dermatophytes were Trichophyton species which were isolated from all the three samples i.e. skin, hair and nail. A majority of the diagnosed patients showed erythematous, scaly annular lesions with raised and inflammatory borders with itching. Mixed infections, which constituted about 3.5%, were a combination of tinea corporis and tinea cruris. Either individually or in mixed infections, these two infections are caused by Trichophyton species. Tinea capitis infections which include ectothrix and endothrix are caused by species of Microsporum and Trichophyton.ConclusionsThe investigations reveal that superficial mycoses are very common in this region. Tinea corporis is the most common clinical manifestation. Majority of the infections are caused by Trichophyton species. Mixed infections constituted a small proportion.     

Otitis media as a presenting complaint in childhood immunodeficiency diseases

Otitis media is one of the most common childhood infections and may result from a variety of underlying problems. Suspicion of immunodeficiency should increase when ear infections are frequent; suppurative; unresponsive to antibiotics; caused by unusual organisms; or seen in the context of other frequent infections, severe eczema, or failure to thrive. Humoral immune deficiencies, particularly with an inability to make antibody to encapsulated organisms, are the immunodeficiencies most likely to cause increased otitis media. Immune system evaluation should concentrate on humoral immunodeficiency disorders, but the presenting history and physical findings also should be considered when designing the work-up. Treating the underlying immune deficiency is usually necessary to adequately control the ear infections.     

Disseminated Sporothrix schenckii infection with arthritis in a patient with acquired immunodeficiency syndrome

Patients with the acquired immune deficiency syndrome are susceptible to a wide spectrum of opportunistic infections. We report a 34-year-old man who developed systemic sporotrichosis involving the skin and joints, and whose illness terminated in subacute encephalopathy and Pneumocystis carinii pneumonia. Fungal arthritis is another infection to which patients with this syndrome are subject.