Management of resistant mucocutaneous herpes simplex infections in AIDS patients: a clinical and virological challenge.

BACKGROUND: The use of highly active antiretroviral therapy (HAART) has been associated with a marked decrease in the prevalence of opportunistic infections in HIV-infected patients. However, chronic mucocutaneous herpes simplex virus (HSV) infection remains a difficult clinical challenge. OBJECTIVE: The aim of the study was to optimize the diagnosis and follow-up of chronic HSV-2 infection in HIV-infected patients and to correlate clinical data with CD4 cell count, in vitro HSV virological resistance and histology. METHODS: A retrospective case series was collected from a specialist out-patient clinic providing consultations to patients with infectious skin diseases. Clinical, biological, virological and histological data were analysed. RESULTS: Seven HIV-infected patients with genital and perianal herpes simplex infection were followed over 10 years. Ulcerative and pseudo-tumoral forms were observed. Lesions occurred at various stages of immune suppression (CD4 counts from 1 to 449 cells/µL). Clinical resistance to conventional anti-herpetic drugs was correlated with the in vitro resistance of HSV in 70% of cases. CONCLUSIONS: Chronic mucocutaneous HSV infection in AIDS patients remains a rare but regularly observed infection in very immunosuppressed patients or those with unstable immunity during HAART. Virological results obtained from mucocutaneous samples were in most cases found to be correlated with clinical evolution and should therefore be used in making decisions on treatment. Despite efficient antiviral therapy, mucocutaneous healing is slow in the majority of cases.

Pemphigus herpetiformis: analysis of the autoantibody profile during the disease course with changes in the clinical phenotype.

BACKGROUND: Pemphigus herpetiformis (PH) is a rare dapsone-responsive variant of pemphigus, characterized by annular and vesiculopustular cutaneous lesions. Most PH serum samples contain autoantibodies against desmoglein (Dsg)1, but not Dsg3, and the presence of the latter is almost invariably associated with mucosal involvement, as predicted based on the 'Dsg compensation theory'. METHODS: We describe a patient with features characteristic of PH with histologically eosinophilic spongiosis who repeatedly tested positive for anti-Dsg3 but not anti-Dsg1 autoantibodies by ELISA. To investigate whether the peculiar clinical phenotype was due to a distinct immunological profile, the patient's serum was tested by ELISA and immunoblotting using recombinant forms of Dsg3. RESULTS: Serum samples were found to have low and high reactivity against the EC1 and the EC4 domains of Dsg3, respectively, whereas the autoantibodies belonged predominantly to the IgG1 and IgG4 subclasses. The overall immunological profile was typical of pemphigus vulgaris. The patient finally developed isolated oral erosions 22 months after initial presentation, without significant changes in the autoantibody profile and of the targeted antigenic sites. CONCLUSIONS: Our patient presented features characteristic of PH. Although circulating anti-Dsg3 antibodies were present, the patient had only cutaneous involvement for a long period. Our findings indicate that the proposed Dsg compensation theory cannot always explain the clinical phenotype, changes in which may occur without apparent modification of the autoantibody profile and antibody specificity. Hence, additional factors, such as Fcgamma-dependent neutrophil activation, may critically affect the clinical presentation of pemphigus.

[Scleroedema adultorum Buschke in a diabetic subject: intravenous immunoglobulin therapy]. / Scléroedème de Buschke chez un diabétique: traitement par immunoglobulines intraveineuses.

BACKGROUND: Scleroedema adultorum Buschke (SB) is a rare disease involving scleroedema of the neck and shoulders. It can extend to the rest of the trunk and the limbs but characteristically spares the extremities. Three types of SB are distinguished: the first is acute and develops after an infectious disease, the second is of insidious evolution and is associated with monoclonal gammopathy, and the third is associated with type 2 diabetes. PATIENTS AND METHODS: We report the case of a type 2 diabetic patient presenting with progressive, oedematous timbering of the trunk associated with impaired mobility, dysphagia and restrictive respiratory syndrome. SB was diagnosed on the basis of clinical presentation and histology. Treatment was mandatory because of the adverse impact of the disease. A therapy that would not worsen the patient's comorbidities had to be chosen. Intravenous immunoglobulins were thus initiated with excellent response as of the first cycle regarding trunk mobility and dysphagia. Cutaneous rigidity improved steadily until the end of treatment (eight cycles). CONCLUSION: Therapeutic abstention is the rule in SB if it has no severe functional repercussions. Nevertheless, there is no clearly indicated treatment once therapy becomes necessary. Control of underlying diabetes usually does not improve the scleroedema and the metabolic syndrome contraindicates most of the treatments reported in the literature. In this article, we suggest a new treatment of SB in the diabetic patient.

Generalized xerotic dermatitis with neutrophilic spongiosis induced by erlotinib (Tarceva).

Erlotinib is a small molecule tyrosine kinase inhibitor that is used as an anticancer agent. Most patients develop a pustular facial dermatitis within the first week of treatment. Pyogenic granulomas of the nail folds are another typical adverse event occurring in about 10-15% of cases. We report on a patient who developed a generalized dermatitis characterized by neutrophilic spongiosis. Neutrophilic inflammation has been observed in several drugs that interfere with EGFR signaling, suggesting a class effect. The present case may be yet another manifestation of this particular reaction pattern.

Sirolimus-induced inflammatory papules with acquired reactive perforating collagenosis.

Sirolimus is an immunosuppressive macrolide with antineoplasic properties that is increasingly used in posttransplantation immunosuppression. The treatment is frequently associated with cutaneous side effects such as sirolimus-associated acneiform facial dermatitis, which has been observed in up to 50% of treated patients. We report a 51-year-old female with liver transplantation who developed inflammatory papules and nodules on the face and the upper chest 3 weeks after the initiation of sirolimus therapy. Sequential biopsies revealed lymphocytic infiltration of the dermis with a peculiar pattern of sebotropism, while older lesions showed acquired reactive perforating collagenosis. The lesions were responsive to hydroxychloroquine treatment despite continued sirolimus treatment.

Amicrobial pustulosis of the folds associated with auto-immune disorders. A case report with an analysis of cytokine expression profile in skin lesions of cutaneous neutrophilic lupus.

A new entity was described by Crickx et al. in 1991, associating amicrobial pustulosis of the folds with systemic lupus erythematosus in young females. It is proposed to regroup this entity under the name of 'neutrophilic cutaneous lupus'. We report a case of a 13-year-old girl with a pustular eruption of the cutaneous folds and scalp associated with undetermined connective tissue disease. We performed a screening for the expression of 174 cytokines in the pustules and compared it with other pustular diseases (acne flare, acute generalized exanthematous pustulosis, pustulosis of Sneddon and Wilkinson). Matrix metalloproteinase 9 and Siglec-5 (CD170) were highly expressed in all types of pustules and reflect high neutrophil density. Amicrobial pustulosis of the folds was characterized by a higher expression of interleukin (IL) 1alpha, IL-2 receptor alpha, macrophage colony-stimulating factor, insulin-like growth factor binding protein 1, brain-derived neurotrophic factor, tumour necrosis factor (TNF) alpha and a lower expression of CD14, IL-1beta, IL-12, soluble TNF receptors I and II, growth-regulated oncogene alpha, fibroblast growth factor 4 and vascular endothelial growth factor as compared to the controls.

Plasminogen activation in melanocytic neoplasia.

A large body of experimental evidence suggests that plasminogen activators provide tumoral cells with efficient means to degrade extracellular matrix constituents and thereby facilitate their dissemination to distant sites. Melanocytic neoplasia encompass a spectrum of lesions exhibiting diverse clinical behavior that remain difficult to predict with current histopathological evaluations. Little information concerning the contribution of plasminogen activation in diagnostic specimens of human melanocytic tumors is presently available. We thus analyzed biopsy specimens of pigmented skin lesions by histological techniques that identify the cellular sites of synthesis of plasminogen activators and of their inhibitors and that localize the sites of plasminogen activators-catalyzed enzymatic activities. We found that urokinase-type plasminogen activators (uPA) and plasminogen activator inhibitor type 1 mRNAs accumulate in atypical nevocytes and in melanoma cells, but not in benign nevocytes. However, uPA-catalyzed proteolytic activity was detected exclusively in melanomas. These observations suggest that up-regulation of the uPA gene is an early feature of melanocyte transformation and that unbalanced enzyme/inhibitor activity is associated with the malignant phenotype. By supporting a role for uPA in melanoma invasiveness, they provide a novel tool for the evaluation of atypia in nevi.

Transformed and nontransformed human T lymphocytes migrate to skin in a chimeric human skin/SCID mouse model.

To study human T cell migration to human skin in vivo, we grafted severe combined immunodeficient mice with 500-microm thick human skin. Two weeks after grafting, epidermal and dermal structures in the grafts were of human origin. When we intraperitoneally injected grafted mice with clones of the human HUT-78 T cell line derived from a patient with cutaneous T cell lymphoma and Sézary syndrome, we detected in the grafts the rare Vbeta23-Jbeta1.2 T cell receptor transcripts characteristic for the HUT-78 clones. These signals were found 2-6 d after cell injection in about 40% of the grafted and HUT-78 cell injected mice but not in grafts from mice that received no exogenous T cells. In contrast to HUT-78 cells, which only accumulate in low number, grafts topically challenged with nickel sufate in vaseline from mice that were injected with autologous nickel-reactive T cell lines led to massive accumulation of T cells within 3 d. Only scattered T cells accumulated in the skin when grafted mice received vaseline plus T cells, nickel sulfate alone, T cells alone, or nickel sulfate plus an allogeneic nickel-nonreactive T cell clone. When the T cell lines were labeled with the fluorochrome PKH-26 before cell injection, spots of fluorescent label in the size and shape of cells were found in the grafts challenged with nickel. Together, these results clearly demonstrate that human T cells can migrate to human skin in this chimeric human/mouse model.

Involvement of granulocytes and the adhesion receptors intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in tissue inflammation induced by Th2-type helper cells.

We reported recently that subcutaneously injected, anti-CD3 epsilon-pulsed polyclonal Th2 cells mediate interleukin-4-dependent local tissue inflammation. Because a prominent polymorphonuclear infiltrate was observed in the lesions at the time of maximal tissue swelling, we investigated the involvement of polymorphonuclear leukocytes and their adhesion molecules lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) in Th2-cell-mediated inflammation. Pretreatment of recipient mice with a depleting monoclonal antibody to neutrophils or with blocking antibodies to LFA-1 or to ICAM-1 completely abrogated tissue swelling in Th2-cell-mediated inflammation. Granulocyte infiltration at 6 h was also inhibited by the antibodies to neutrophils and to ICAM-1, but not by that to LFA-1. Tissue swelling mediated by Th1 cells had different kinetics and was not prevented by administration of anti-neutrophil antibody: maximal edema formation occurred at 24-48 h, when the predominant cellular infiltrate was mononuclear. Because the Th1-cell-induced infiltrate at 6 h also consisted of granulocytes but was not associated with pronounced edema, the mere presence of infiltrating polymorphonuclear leukocytes seems not to be sufficient to induce edema. Because edema but not granulocyte infiltration was inhibited by anti-LFA-1 and because anti-LFA-1 antibodies are known to inhibit several functions of neutrophils, our results suggest that, in inflammation mediated by Th2 cells, granulocytes induce edema through their activation and/or degranulation.

Topical retinaldehyde on human skin: biologic effects and tolerance.

The present study was designed to explore if *etinaldehyde, a natural metabolite of vitamin A, has any biologic activity and is tolerated by human skin. Biologic activity was shown by the induction of cellular retinoic acid-binding protein type 2 (CRABP 2) mRNA and protein; the rank order for CRABP-2 increase was retinoic acid > retinaldehyde > 9 cis retinoic acid > retinol > beta carotene. In volunteers treated 1-3 months with 0.5, 0.1, and 0.05% retinaldehyde, there was a dose-dependent and significant increase in epidermal thickness, keratin 14 immunoreactivity, and Ki67-positive cells. The area of distribution of involucrin, transglutaminase, and filaggrin immunoreactivity was also increased in a dose-dependent manner, and keratin 4 immunoreactivity was induced in the upper epidermis. In pilot clinical tolerance studies, 229 patients received topical retinaldehyde at different concentrations; the 1% preparation was tolerated by up to 70% of the treated subjects; tolerance of the 0.5% preparation was slightly better, whereas both 0.1 and 0.05% preparations applied on facial skin were well tolerated and allowed prolonged use (up to 3 years) in patients with inflammatory dermatoses. These findings indicate that topical retinaldehyde has biologic activity and is well tolerated on human skin.

Post-stripping sclerodermiform dermatitis.

BACKGROUND: Cutaneous sclerosis, a process that results in hardening of the skin, is the hallmark of scleroderma and sclerodermoid disorders. Cutaneous sclerosis is usually classified as secondary or primary, depending on the presence or absence of underlying diseases. Primary cutaneous sclerosis is a feature of idiopathic inflammatory processes that are often associated with autoimmune disorders, whereas secondary cutaneous sclerosis arises in the context of many pathological processes of varying causes, including chronic graft-vs-host disease, defined metabolic or genetic disorders, and exposure to certain infectious organisms, drugs, or chemicals. OBSERVATIONS: Three patients had localized cutaneous sclerosis overlying the site of a surgically removed (stripped) great saphenous vein. In all 3 patients, lesions were clinically characterized by multiple hypopigmented and indurated plaques distributed linearly along the path of the preexisting vein. Extensive history, physical examination, and diagnostic tests did not reveal known predisposing factors for cutaneous sclerosis. CONCLUSIONS: Although the observed association of sclerodermiform dermatitis and venous stripping in these 3 patients does not imply a causal relationship, the absence of other identifiable predisposing factors and the striking linear distribution of the cutaneous lesions along the path of the preexisting vein are suggestive. This poststripping sclerodermiform dermatitis may be a rare late complication of saphenous vein stripping.

Congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis is an autosomal-recessive disorder resulting from defective neural crest differentiation with loss of the first-order afferent system, which is responsible for pain and temperature sensation. There is also a neuronal loss in the sympathetic ganglia. Lack of sweating, hyperthermia, and infections of bones are main features of the disorder; however, contradictory results have been published regarding eccrine sweat gland innervation. A 5-year-old male patient with typical clinical manifestations of congenital insensitivity to pain with anhidrosis is presented. Immunohistochemistry with antibodies against S100 protein and neuron-specific enolase failed to reveal nerve fibers in the vicinity of the eccrine sweat glands. The roles of the nerve growth factor and tyrosine kinase receptor gene mutations in the pathogenesis of the disease are also discussed.

[Solid persistent facial edema of the young adult. Melkersson-Rosenthal syndrome]. / Oedème facial solide persistant du sujet jeune. Syndrome de Melkersson-Rosenthal.

We report a case of solid persistent facial oedema in a 18-year-old woman. A biopsy specimen from the nose demonstrating lympho-epithelioid granulomas and an electro-neuro-myographic examination revealing sub-clinical sequellae from an old right facial palsy, led to the definite diagnosis of Melkersson-Rosenthal syndrome (MRS). We focus on the differential diagnosis of persistent facial oedema and outline the difficulties to establish the diagnosis of MRS when all features of the classic triad "recurrent labial edema-facial nerve palsy-lingua plicata" are not present.

[Schoenlein-Henoch syndrome in adults--current aspects]. / Le syndrome de Schoenlein-Henoch de l'adulte--aspects actuels.

Schoenlein-Henoch purpura is characterized clinically by palpable purpura, mainly on the legs, with varying degrees of gastrointestinal, articular and renal involvement. Renal involvement is often more severe in the adult than in children and it often determines the outcome of the disease. Schoenlein-Henoch purpura is also characterized by an IgA-vasculitis, which may be triggered by several non-specific antigenic factors. Its pathogenesis is still unclear, but a dysfunction of the IgA immune system has been demonstrated. We discuss the anatomo-clinical, therapeutic and etiopathogenic aspects of this syndrome according to today's knowledge.