Staphylococcus aureus has long been recognized as an important pathogen in human disease. Due to an increasing number of infections caused by methicillin-resistant S. aureus (MRSA) strains, therapy has become problematic. Therefore, prevention of staphylococcal infections has become more important. Carriage of S. aureus appears to play a key role in the epidemiology and pathogenesis of infection. The ecological niches of S. aureus are the anterior nares. In healthy subjects, over time, three patterns of carriage can be distinguished: about 20% of people are persistent carriers, 60% are intermittent carriers, and approximately 20% almost never carry S. aureus. The molecular basis of the carrier state remains to be elucidated. In patients who repeatedly puncture the skin (e.g., hemodialysis or continuous ambulatory peritoneal dialysis [CAPD] patients and intravenous drug addicts) and patients with human immunodeficiency virus (HIV) infection, increased carriage rates are found. Carriage has been identified as an important risk factor for infection in patients undergoing surgery, those on hemodialysis or CAPD, those with HIV infection and AIDS, those with intravascular devices, and those colonized with MRSA. Elimination of carriage has been found to reduce the infection rates in surgical patients and those on hemodialysis and CAPD. Elimination of carriage appears to be an attractive preventive strategy in patients at risk. Further studies are needed to optimize this strategy and to define the groups at risk.

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Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks.

Staphylococcus aureus is a frequent cause of infections in both the community and hospital. Worldwide, the increasing resistance of this pathogen to various antibiotics complicates treatment of S aureus infections. Effective measures to prevent S aureus infections are therefore urgently needed. It has been shown that nasal carriers of S aureus have an increased risk of acquiring an infection with this pathogen. The nose is the main ecological niche where S aureus resides in human beings, but the determinants of the carrier state are incompletely understood. Eradication of S aureus from nasal carriers prevents infection in specific patient categories-eg, haemodialysis and general surgery patients. However, recent randomised clinical trials in orthopaedic and non-surgical patients failed to show the efficacy of eliminating S aureus from the nose to prevent subsequent infection. Thus we must elucidate the mechanisms behind S aureus nasal carriage and infection to be able to develop new preventive strategies. We present an overview of the current knowledge of the determinants (both human and bacterial) and risks of S aureus nasal carriage. Studies on the population dynamics of S aureus are also summarised.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(05)70295-4.pdf

The role of nasal carriage in Staphylococcus aureus infections.

Iontophoretic drug delivery

Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis (phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors) in bone marrow and other tissues. HLH may be diagnosed in association with malignant, genetic, or autoimmune diseases but is also prominently linked with Epstein-Barr (EBV) virus infection. Hyperproduction of cytokines, including interferon-gamma and tumor necrosis factor-alpha, by EBV- infected T lymphocytes may play a role in the pathogenesis of HLH. EBV-associated HLH may mimic T-cell lymphoma and is treated with cytotoxic chemotherapy, while hemophagocytic syndromes associated with nonviral pathogens often respond to treatment of the underlying infection.

/pdf/hemophagocytic-syndromes-and-infection-2aj9a8bz14.pdf

Hemophagocytic syndromes and infection.

Human cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8 + T cells with peptide-HLA tetrameric complexes, we have demonstrated high levels of antigen-specific cells specific for HCMV peptides and show that this may exceed 4% of CD8 + T cells in immunocompetent donors. Moreover, by staining with tetramers in combination with antibodies to cell surface markers and intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific populations. A substantial proportion of these are effector cytotoxic T lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in “fresh” killing assays. These data suggest that the immune response to HCMV is periodically boosted by a low level of HCMV replication and that sustained immunological surveillance contributes to the maintenance of host-pathogen homeostasis. These observations should improve our understanding of the immunobiology of persistent viral infection.

Functional Heterogeneity and High Frequencies of Cytomegalovirus-Specific CD8+ T Lymphocytes in Healthy Seropositive Donors

Background: Cutaneous disease is common in patients infected with HIV-1. Objective: The aim of our study was to identify cutaneous markers associated with HIV-1 infection and disease progression as measured by Walter Reed (WR) stage. Methods: For 42 months we have observed 912 HIV-1-positive patients in all WR stages. All patients had an extensive past and present medical history taken as well as a complete physical examination, periodic visits, and appropriate diagnostic procedures. Results: Increasing dryness of the skin and seborrheic dermatitis are early findings in a large percentage of patients in WR stage 1; the occurrence and severity of both conditions increase with disease progression. Tinea infections, condylomata acuminata, and Verrucae are seen early, but with disease progression, although there is no clear increase in occurrence, these infections become more diffuse and resistant to treatment. Flares in acne vulgaris and folliculitis show a peak occurrence in early and mid-stage disease with a decreased occurrence in late-stage disease. Herpes simplex infections, oral candidiasis, molluscum contagiosum, Staphylococcus aureus infections, and oral hairy leukoplakia show a marked increase in occurrence with advanced disease. Conditions that have a statistically significant association with disease progression as measured by a change in stage include drug eruptions, seborrheic dermatitis, oral candidiasis, oral hairy leukoplakia, molluscum contagiosum, herpes zoster, and hyperpigmentation (nail, oral, skin). Conclusion: The most frequent and persistent cutaneous disorders were asteatosis (with or without asteatotic eczema) and seborrheic dermatitis. Conditions that were associated with a change in WR stage include drug eruptions, seborrheic dermatitis, oral candidiasis, oral hairy leukoplakia, molluscum contagiosum, herpes zoster, and hyperpigmentation. In addition to Kaposi's sarcoma, patients with HIV-1 disease have an increased potential for the development of both cutaneous epithelial and probably melanocytic malignancies. Epithelial tumors were seen in patients in all stages of disease.

Cutaneous findings in HIV-1-positive patients: A 42-month prospective study

Although molluscum contagiosum virus (MCV) is considered by some as an unclassified poxvirus, others consider it a member of the orthopoxvirus genus, family Poxiviridae. It is a large double-stranded DNA virus that has a worldwide distribution. With the eradication of small pox, variola virus (VAR), MCV remains by far the most common pox viral pathogen for humans.1–6 Lesions of MCV occur almost exclusively in the skin, and only rare reports have referred to mucous membrane lesions.1–3 Lesions of MCV are most commonly seen in young children, sexually active adults, and in some immune suppressed patient populations (Figs 1–5). Although MCV infections are highest in warm moist climates, and in populations where personal hygiene is difficult to maintain, they have a worldwide distribution.1–3 In children, MCV has a diffuse distribution and may occur on the face, trunk, and extremities, as well as in the genital area (Fig. 1).1–4 In young adults, sexual contact is probably the most common mode of transmission, and genital lesions are common (Fig. 2).1–4 In human immunodeficiency virus type 1-positive (HIV-11) patients, widespread lesions do occur, but head and neck lesions are most common, followed by genital involvement.1–4,7,8 Although the typical umbilicated papules occur in all patient populations, in HIV-11 patients, verrucous, warty papules, as well as giant molluscum greater than 1 cm in diameter, are also seen (Figs 3–5).1–4,7,8 In patients without severe immune suppression, lesions produced by MCV typically regress spontaneously usually within months, rarely years.1–6,9 MCV cannot be grown in tissue culture cells and does not infect animals; however, it has been replicated in human skin grafted to immune deficient mice.5,6,9 MCV is only distantly related to VAR, and lacks DNA cross-hybridization or immunologic cross-reactivity.5,6,9 Four major subtypes of MCV have been defined by recent work, including three MCV-1 variants and MCV-2, MCV-3, and MCV-4 subtypes.9 MCV-1 subtypes dominate worldwide and, in one report, MCV-1 subtypes occurred exclusively in children under the age of 15 years;2,3,10 however, there is evidence that other MCV subtypes are more common in the HIV-11 patient population.3,11 In the light of the new molecular information available on MCV, we returned to review the clinical and histologic features seen in both HIV11 and HIV-1– individuals.

Molluscum contagiosum: its clinical, histopathologic, and immunohistochemical spectrum

Background: Tissue-destructive and more selective cytotoxic therapies are the main methods used to treat actinic cheilitis. A topical immune stimulant, 5% imiquimod cream, has recently been used for treatment of cutaneous epithelial malignancies including squamous cell carcinoma in situ and basal cell carcinoma. Objective: Our aim was to review the results in patients who had been treated for actinic cheilitis with imiquimod cream. Methods: A review identified 15 patients with biopsy-proven actinic cheilitis who had been treated with topical imiquimod 3 times weekly for 4 to 6 weeks. All patients with histories consistent with facial herpes simplex or documented prior facial herpes simplex eruptions were treated with oral valcyclovir, 1 g/d, during imiquimod therapy. Results: All 15 patients showed clinical clearing of their actinic cheilitis at 4 weeks after discontinuation of the topical imiquimod. Sixty percent of the patients experienced a moderate to marked increased local reaction consisting of increased erythema, induration, and erosions or ulcerations, which in some cases continued through the period of therapy. Conclusion: Imiquimod appears to have a role in the treatment of actinic cheilitis. However, the dose and duration of therapy, as well as the long-term efficacy, need to be established; and local reactions are to be expected and may not improve during therapy. (J Am Acad Dermatol 2002;47:497-501.)

https://www.jaad.org/article/S0190-9622(02)00087-7/pdf

Topical 5% imiquimod for the therapy of actinic cheilitis.

• Background and Design.— The hemophagocytic syndrome (HPS) is characterized by fever, wasting, generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia, often with associated coagulopathy. The most common cutaneous manifestations are panniculitis and purpura. Cytophagic histiocytic panniculitis fits within the spectrum of HPS, and the most consistent histopathologic feature in HPS is a proliferation of mature histiocytes that exhibit prominent erythrophagocytosis and cytophagocytosis. The clinical spectrum, the underlying causes, and the histopathologic features found in HPS are broad. The characteristic phagocytic histiocytes seen in HPS have been confused with malignant histiocytes in the past, but are now known to be reactive. The clinical findings, histologic, and immunohistochemical features of 10 cases of HPS with cutaneous lesions were reviewed. Immunohistochemical markers included KP-1, βF-1, UCHL-1, L-26, MAC-387, factor XIIIa, and S100 protein. Results.— The HPS was associated with T-cell lymphoma and/or viral infection. Most biopsy specimens showed edema and hemorrhage with a lymphohistiocytic infiltrate and prominent histiocytic cells showing erythrophagocytosis and, in some cases, cytophagocytosis. The histiocytic cells showed positive reactions for KP-1 and negative reactions for the lymphoid markers. In all cases the lymphoid cells showed a mixed pattern with most cells positive for βF-1 and UCHL-1, and a small percentage positive for L-26. Conclusion.— In HPS, the prominent phagocytic histiocytes are reactive and are stimulated by T-cell lymphocytes, either neoplastic or in response to viral infection. Many of the findings in the HPS may also be due directly or indirectly to cytokines produced by proliferating T-cell lymphocytes and/or reactive phagocytic histiocytes. ( Arch Dermatol. 1992;128:193-200)

Cutaneous Histopathologic, Immunohistochemical, and Clinical Manifestations in Patients With Hemophagocytic Syndrome

Background: In HIV-1-positive patients there have been no prospective studies that show an increase in cutaneous neoplasms. Objective: We observed HIV-1-positive patients to determine whether or not there was an increased incidence of cutaneous malignancies. Methods: A total of 724 HIV-1-positive patients were examined during a 36-month period for the development of cutaneous malignancies. Results: The most common cutaneous neoplasm found was Kaposi's sarcoma, especially in patients with late-stage disease. Basal cell carcinomas were the next most frequent tumor. We have also seen three malignant melanomas and two squamous cell carcinomas. Five patients had malignant lymphoma. One patient had a primary lymphoma of subcutaneous soft tissue; in one patient multiple cutaneous lesions developed. Conclusion: The distribution and prevalent types of cutaneous neoplasms in HIV-1-positive patients appear to differ from those found in other immunosuppressed populations. This may be the result of the different patterns and periods of immunosuppression in these patients and/or associated cocarcinogens to which these patients frequently are exposed.

Josef Yeager

Papers

Cutaneous findings in HIV-1-positive patients: A 42-month prospective study

Molluscum contagiosum: its clinical, histopathologic, and immunohistochemical spectrum

Topical 5% imiquimod for the therapy of actinic cheilitis.

Cutaneous Histopathologic, Immunohistochemical, and Clinical Manifestations in Patients With Hemophagocytic Syndrome

Cutaneous neoplasms in a military population of HIV-1-positive patients******