Clinical and cytologic features of antibiotic-resistant acute paronychia.

BACKGROUND: Acute paronychia usually is treated as a bacterial infection, but antibiotic-resistant acute paronychia may be caused by other infectious and noninfectious problems. OBJECTIVE: We sought to describe the clinical, etiologic, cytologic, and therapeutic features of antibiotic-resistant acute paronychia. METHODS: A retrospective review of medical records and cytology was performed in 58 patients (age, 1 month-91 years; 36 children and adolescents [62%] and 22 adults [38%]) who had antibiotic-resistant acute paronychias. RESULTS: Causes of paronychia included bacteria (25 patients [43%]), viruses (21 patients [36%]), fungi (5 patients [9%]), drugs (3 patients [5%]), pemphigus vulgaris (3 patients [5%]), and trauma (1 patient [2%]). Diagnostic cytologic findings were noted in 54 patients (93%); no diagnostic cytologic findings were present with drug-induced (3 patients) or traumatic (1 patient) paronychia. The most common predisposing factors were the habits of finger- or thumb-sucking (14 patients [24%]) and nail-biting (11 patients [19%]). Complications included id reaction with erythema multiforme in 3 patients (5%). LIMITATIONS: Limitations include retrospective study design from 1 treatment center. CONCLUSION: Antibiotic-resistant acute paronychia may be infectious or noninfectious. Cytologic examination with Tzanck smear may be useful diagnostically and may prevent unnecessary use of antibiotics and surgical drainage.

Viruses and pemphigus: an intriguing never-ending story.

Virus infections and autoimmunity have long been linked. As to pemphigus, many studies have been directed to prove or rule out the possibility of viral induction. Herpesviruses have often been related to the onset or reactivation of pemphigus. The association may be (i) casual, (ii) due to the iatrogenic immunosuppression facilitating opportunistic viral infections or (iii) based on a pathogenic link between the viral presence and the host's dysregulated immune response leading to autoimmunity. Japanese researchers, using real-time polymerase chain reaction, lately detected herpes simplex virus DNA in the saliva from pemphigus patients at the earliest stage of the disease and with no signs or history of herpetic infection, thus confirming the possible existence of cases of pemphigus induced by herpesviruses. These selected cases could be included into the innovative concept of 'paraviral eruptions', where an inciting role for induction may be played by the concomitant intake of certain drugs.

Monolesional Kaposi sarcoma at the site of slow healing herpes zoster in an HIV+ patient: immunocompromised district in an immunocompromised patient.

Besides the well-known systemic immune deficiency, also a regional immune deficiency, labeled as "immunocompromised district" (ICD), has been documented and focused in the recent years. The objective of the study is to gain more insights into the mechanisms involved in systemic and local immune destabilization. A 35-year-old, homosexual, and drug-addicted HIV+ man presented with a single nodule of Kaposi sarcoma (KS) located on the penis, where a slow to heal herpes zoster had appeared 2 months before. It has been assumed that the unusual penile location of herpes zoster facilitated the outbreak of KS in the affected dermatome because of a viral damage to sensory nerve fibers of the same dermatome. This damage, by interfering with the immunoregulatory function of neuropeptides released by nerve endings in that area, may have caused a regional alteration of the immune control favoring the local onset of the "opportunistic" angiogenic tumor (KS). In a few words, an ICD took place in an immunocompromised patient, thus introducing a more vulnerable site in an already vulnerable subject. The present case is the second one in the literature to document an ICD in the setting of preexisting systemic immune deficiency.

Beyond zoster: sensory and immune changes in zoster-affected dermatomes: a review*.

Neuroepidermal tropism of varicella-zoster virus accounts for cutaneous and nerve lesions following herpes zoster. Skin lesions heal in a few weeks and may or may not leave visible scars. Nerve lesions involve peripheral sensory fibres, sometimes causing permanent damage that results in partial denervation of the affected dermatome. The effects of the nerve injury involve the sensibility function, thus causing neuralgia, itch, allodynia, hypo- or anaesthesia, as well as the immune function that is related to neuropeptide release, thus altering immune control in the affected dermatome. The neuro-immune destabilization in the zoster-infected site paves the way for the onset of many and various immunity-related disorders along the affected dermatome.

MDM2 and CDKN1A gene polymorphisms and risk of Kaposi's sarcoma in African and Caucasian patients.

A single-nucleotide polymorphism in the MDM2 promoter (SNP309; rs2279744) causes elevated transcription of this major negative regulator of p53 in several cancer types. We investigated MDM2 SNP309 and CDKN1A (p21/Waf1/Cip1) codon 31 (rs1801270) polymorphisms in 86 cases of cutaneous Kaposi's sarcoma (KS) from African and Caucasian patients, and 210 healthy controls. A significant increase of the MDM2 SNP309 T/G genotype was observed among classic KS cases (odds ratio 2.38, 95% confidence interval 1.0-5.5). Frequencies of CDKN1A codon 31 genotypes were not significantly different between cases and controls. The results suggest that the MDM2 SNP309 G allele may act as a susceptibility gene for the development of classic KS in Caucasian patients.

Kaposi sarcoma and quinine: a potentially overlooked triggering factor in millions of Africans.

Kaposi sarcoma (KS)-associated herpesvirus, also known as human herpesvirus 8, is necessary but not sufficient for the development of KS. Lytic reactivation of human herpesvirus 8 may be important in KS pathogenesis. KS and its causative agent, KS-associated herpesvirus, have distinctive largely unexplained geographic distributions. We note the recent "oncoweed" hypothesis of biologic plants in the environment accounting for this reactivation. We believe that quinine and its derivatives might better explain the epidemiology of KS than oncoweeds. Indeed, we propose an "oncodrug" hypothesis, specifically with regard to quinine and its derivatives, a linkage first advanced by one of us (V. R.) and associates in 1984.

TP53 codon 72 polymorphism in classic, endemic and epidemic Kaposi's sarcoma in African and Caucasian patients.

OBJECTIVES: Several studies have examined the association of codon 72 polymorphism of the TP53 gene, encoding either arginine or proline, in several tumor types but none have investigated its role in Kaposi's sarcoma (KS) development. METHODS: In this prevalent case-control study, 67 cutaneous lesions of classic, iatrogenic, endemic as well as epidemic KS from African (n = 22) and Caucasian (n = 45) patients, and blood samples from 150 healthy controls (n = 57 African, n = 93 Caucasian) have been analyzed for arginine and proline allele distribution. RESULTS: Among African cases the proline homozygous, heterozygous and arginine homozygous genotype frequencies were 50.0, 31.8 and 18.2%, respectively, and among controls 54.4, 40.3, and 5.3%, respectively (p = 0.1872). Conversely, among Caucasian cases genotype distributions were 6.7, 55.6, and 37.8%, and among controls 7.5, 34.4, and 58.1%, respectively (p = 0.0567). No significant differences in arginine and proline allele distribution were observed when the cases were stratified by HIV status/tumor type. CONCLUSIONS: The results obtained in this study suggest that p53 polymorphism at codon 72 does not represent a risk factor for the development of all forms of KS, either among African or among Caucasian populations.

Searching for experimental models of Pemphigus vulgaris.

The current knowledge on Pemphigus vulgaris (PV) pathophysiology suggests that blister formation relies on both PV IgG and non-IgG serum factors activity. PV autoimmunity seems to develop against both desmoglein 1/3 and acetylcholine receptors leading to transduction of signals to the cell mediated by phosphorilation events. Serum factors other than IgG also participate to PV acantholysis through apoptotic or cytokine-mediated mechanisms. Apart from the role played by each actor within the acantholysis, however, the current scenario arises important methodological issues. For example, the use of PV IgG or monoclonal anti-Dsg3 antibodies to experimentally reproduce the disease appears inadequate, as it does not take into account the role of non-IgG factors. On the basis of the above observations and those from our laboratories, here we propose that using whole sera from PV patients with active disease represents the most faithful manner to mimic the disease.

Vesicular and bullous disorders: pemphigus.

Pemphigus is a chronic, autoimmune disease involving the skin and Malpighian mucous membranes. Pemphigus leads to progressive blistering and subsequent erosions. This article describes the etiology and treatment of pemphigus.

Crohn's disease and its mucocutaneous involvement.

Crohn's disease (CD) is a chronic inflammatory disorder primarily affecting the lower gastrointestinal tract but potentially involving the skin, musculoskeletal system, and eyes. The origin remains unknown, although diverse etiologic agents have been proposed. Characteristic pathologic appearances include the formation of "skip" lesions (discrete regions of inflamed bowel separated by uninvolved mucosae), aphthous ulceration, and fistulation; these signs relate to the presence of an underlying granulomatous transmural inflammation. Cutaneous and oral lesions frequently occur in CD. They may be classified as specific manifestations (in particular, perianal fissures, abscesses, sinuses, and fistulae in ano) with a granulomatous noncaseating inflammation on histologic examination, and nonspecific manifestations (eg, erythema nodosum, neutrophilic dermatoses) with a nonspecific histologic pattern. The diagnosis of CD is based on clinical, endoscopic, radiologic, and histopathologic features. Therapy is mainly aimed at the control of the acute disease and prevention of relapse through the use of mesalazine, corticosteroids, immunosuppressive agents and very recently, anti-tumor necrosis factor-alpha antibodies.

A possible mechanism for phenol-induced pemphigus.

A possible mechanism for phenol-induced pemphigus lesions in genetically predisposed individuals is proposed that accounts for in vitro observations and cases of biochemical acantholysis, as well as the in vivo acantholysis in pemphigus induced by phenols. The mechanism involves the induction of interleukin-1a and tumor necrosis factor-a release by keratinocytes. These cytokines in turn have been shown to be involved in the regulation and synthesis of complement and proteases like plasminogen activator, which have been implicated in the pathogenesis of acantholysis in pemphigus vulgaris.

Life-threatening bullous dermatoses: Pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis with a high mortality rate if untreated. The disease results from autoimmunity to normal components of keratinocyte cell membrane (desmogleins 3 and 1) belonging to the cadherin supergene family. Standard therapy for PV is based on a combined administration of high-dosed glucocorticoids and immunosuppressive drugs. In patients with severe, life-threatening, or recalcitrant PV, stronger therapeutic options should be considered, such as 'pulse-therapy' with discontinuous intravenous infusion of megadoses of immunosuppressive drugs over a short-time, plasmapheresis, and extracorporeal immunoadsorption of pathogenic autoantibodies using the extracellular domain of the PV main antigen (desmoglein 3) produced by baculovirus or, more recently, a tryptophan-linked polyvinyl alcohol adsorber.

The putative role of apoptosis in the induction of pemphigus.

The apoptotic cell has recently been shown to play a central role in tolerizing B cells and T cells to both tissue-specific and ubiquitously expressed self-antigens, and to possibly drive the autoimmune response in systemic lupus erythematosus, an autoimmune disease which bears many similarities to pemphigus. We now propose a similar mechanism in the induction of pemphigus, namely, that a dysregulation in apoptosis expressed as an impairment of normal programmed cell death of epidermal keratinocytes and/or deficient and inadequate clearance of apoptotic material (specifically, desmoglein) may render it antigenic with the consequent production of autoantibodies. The fact that some thiol-containing compounds which are well-known inducers of acantholysis in vitro and pemphigus in vivo were shown to inhibit apoptosis might support our hypothesis.

Pemphigus vegetans of the folds (intertriginous areas).

Pemphigus vegetans (P Veg), the rarest form of pemphigus, is thought to be a variant of pemphigus vulgaris (PV). Classically, two subtypes of P Veg are recognized: (1) Neumann P Veg, which usually begins as PV with vesicles and bullae that rupture to form hypertrophic granulating erosions, then evolving into vegetating exuding masses; (2) Hallopeau P Veg, initially characterized by pustular lesions that, after rupturing, merge and gradually evolve into vegetating erosions with a centrifugal expansion. The disease typically affects the big folds (axillary, inframammary, inguinocrural, intergluteal), where semiocclusion, maceration, and mixed infections continuously incite exudation and granulation tissue formation (wet P Veg). In nonintertriginous locations, the vegetating buttons can dry out to change into warty, fissured, painful, seborrheic keratosis-like lesions (dry P Veg). Histologic examination indicates hyperplastic epidermis with intramalpighian leukocyte microabscesses and indistinct traits of suprabasal acantholysis. Immunofluorescence findings are similar to those of PV. Diagnosis is straightforward when PV lesions coexist. Difficulties can arise in cases with nonflexural location. Cytology (Tzanck test), histology, immunofluorescence, and ELISA search for anti-desmoglein antibodies are the diagnostic laboratory tools. Systemic treatment is similar to that for PV, high-dose steroids being the first choice therapy. Immunosuppressive agents and etretinate may allow a steroid-sparing effect. Topical treatment is aimed at countering the granulation tissue formation by means of several strategies (sublesional steroid injection, application of medicated gauzes in the involved flexures, chemical cautery or surgical excision of vegetating lesions).

Cutaneous sarcoidosis: an intriguing model of immune dysregulation.

Sarcoidosis is a systemic granulomatous disease characterized by the presence of non-caseating granulomas. Its etiology remains obscure. A plausible hypothesis suggests that a complex interplay of host factors, infectious processes, and non-infectious environmental factors, matched with a susceptible genetic background, results in a pathway that leads to systemic granulomatous inflammation. Although presentations of sarcoidosis vary enormously, multi-organ involvement is a common feature. Cutaneous involvement occurs in about 25% of patients with protean manifestations and variable prognoses. Skin manifestations are divided into specific lesions with histopathologically evident non-caseating granulomas and nonspecific lesions arising from a reactive process that does not form granulomas. A peculiar form of cutaneous sarcoidosis is represented by sarcoidal lesions at sites of trauma that has caused scarring. The pathogenesis of scar sarcoidosis remains unknown. Scar sarcoidosis is also associated with herpes zoster infection, surgery, and tattooing. Such heterogeneous events, along with those at the sites of chronic lymphedema, thermal burns, radiation dermatitis, and vaccinations, occur on areas of vulnerable skin labeled "immunocompromised districts". Numerous options are available for the treatment of cutaneous sarcoidosis. Although corticosteroids remain the treatment of choice for initial systemic therapy, other nonsteroidal agents have proven effective and therefore useful for long-term management. Tumor necrosis factor-α antagonists such as infliximab may have a role in the treatment of cutaneous sarcoidosis, especially in refractory cases that are resistant to standard regimens. Elucidation of the relationship of sarcoidal granulomas with malignancy and immunity may facilitate a better understanding of some pathomechanisms operating in neoplastic and immunity-related disorders.

Quinine sulfate and bacterial invasion.

BACKGROUND: As many patients who receive antimalarial drugs for treatment of noninfectious, inflammatory diseases are also immunosuppressed and might have a concomitant bacterial infection, we studied the effectiveness of these drugs against bacterial infections, to find out whether they could protect against (and even treat) such conditions and obviate the need for an additional antibiotic drug. METHODS: Effect of QS on bacterial growth: Escherichia coli (E. coli) HB101 pRI203 were cultured overnight at 37 degrees C in TSB and inoculated (approx 1 x 10(7) cells/ml) in MEM in the presence of QS at various concentrations (0, 50 and 100 microM).The effect of QS at concentration of 50 and 100 microM on the entry process of E. coli HB101 pRI203 into HeLa cells was studied under different experimental conditions: 1. QS was incubated with 3 x 10(5) HeLa cells for 60 min at 37 degrees C prior to infection. 2. QS was added to HeLa cell monolayers during the infection period. RESULTS: QS showed no antibacterial activity after 24 h of incubation. The invasive efficiency of the bacteria was significantly inhibited at a dose-dependent manner, when QS was added to HeLa cells for 60 min at 37 degrees C prior to infection (condition 1), and to a lesser extent when added during the period of infection (condition 2). CONCLUSIONS: Although the antimalarials are generally regarded as being inactive against most extracellular bacterial species, our results indicate that QS significantly inhibited the internalization/invasion efficacy of E. coli in the host cells.