Chronic itch induced by thalamic deep brain stimulation: a case for a central itch centre.

BACKGROUND: Central itch syndrome has been previously described in conditions such as stroke. The neurophysiology of central itch syndrome has been investigated in non-human primates but remains incompletely understood. METHODS: We report an observational study of a rare case of severe central itch following thalamic deep brain stimulation and postulate the location of the central itch centre in humans. RESULTS: The patient was a 47-year-old female, with congenital spinal malformations, multiple previous corrective spinal surgeries and a 30-year history of refractory neuropathic pain in her back and inferior limbs. Following multidisciplinary pain assessment and recommendation, she was referred for spinal cord stimulation, but the procedure failed technically due to scarring related to her multiple previous spinal surgeries. She was therefore referred to our centre and underwent bilateral deep brain stimulation (DBS) of the ventral posterolateral nucleus of the thalamus for management of her chronic pain. Four weeks after switching on the stimulation, the patient reported significant improvement in her pain but developed a full body progressive itch which was then complicated with a rash. Common causes of skin eczema were ruled out by multiple formal dermatological evaluation. A trial of unilateral "off stimulation" was performed showing improvement of the itchy rash. Standard and normalized brain atlases were used to localize the active stimulating contact within the thalamus at a location we postulate as the central itch centre. CONCLUSIONS: Precise stereotactic imaging points to the lateral portion of the ventral posterolateral and posteroinferior nuclei of the thalamus as critical in the neurophysiology of itch in humans.

Ten cases of drug reaction with eosinophilia and systemic symptoms (DRESS) treated with pulsed intravenous methylprednisolone.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, life-threatening, drug-induced illness characterised by a widespread polymorphic eruption, fever and multivisceral involvement. There is little published on the management of DRESS. Prompt recognition and withdrawal of the causative drug is essential, along with supportive treatment. However, the condition commonly progresses despite these measures. Oral corticosteroids are usually given but the response can be suboptimal and result in a prolonged exposure to systemic glucocorticoid. We conducted a prospective single-centre study to determine the efficacy of pulsed intravenous methylprednisolone followed by a short reducing course of oral prednisolone in ten patients with confirmed DRESS. Rash and fever responded rapidly to methylprednisolone in all patients. Compared to pre-treatment assessments, there was a significant reduction in eosinophil count at day 14 and AST level at day 90 post-treatment. One patient developed acute hepatic failure, necessitating a liver transplant, and died 4 months later. In the immediate post-treatment phase, 1 patient developed type 1 diabetes and 1 patient developed a corticosteroid-induced psychosis. Long-term follow-up on 8/10 revealed all patients to be well, although one patient had persistent pruritus. An aggressive corticosteroid regimen in the management of DRESS is associated with good clinical outcome and acceptable tolerance.

A retrospective study of the management of pediatric kerion in Trichophyton tonsurans infection.

Kerion celsi is the inflammatory extreme of tinea capitis, representing a delayed hypersensitivity reaction to the causative dermatophyte. Some authors have advocated the use of oral corticosteroids in patients with kerion formation to inhibit the host inflammatory response and minimize the risk of scarring. This retrospective study analyzed the management and outcome of all children younger than 10 years old presenting to our pediatric dermatology service with tinea capitis resulting in kerion formation between 2003 and 2009. We propose that kerion treatment be directed toward the underlying dermatophyte. Oral and intralesional corticosteroids are an unnecessary adjunct to oral antifungal therapy for children with tinea capitis presenting with kerion in urban areas.

Cutaneous manifestations of infections: an update for general physicians.

Infection rashes can present in a number of different ways, some giving a reactive pattern in the skin to infection elsewhere in the body, while others reflect infection within the affected skin itself. Recognising the possible systemic symptoms, characteristic distribution and morphology of rashes can lead to a high degree of accuracy in making a clinical diagnosis in the clinic room/at the bedside that can be confirmed with a few simple laboratory tests.

Production of melanin by Aspergillus fumigatus.

Melanins, or melanin-like compounds, may play a role in the pathogenesis of a number of human fungal infections. This study investigated the production of melanin by the important opportunistic pathogen Aspergillus fumigatus. Conidia from A. fumigatus were harvested and treated with proteolytic enzymes, denaturant and hot, concentrated acid; this yielded dark particles which were similar in size and shape to the original propagules. Electron spin resonance spectroscopy revealed that the conidial-derived particles were stable free radicals consistent with an identification as melanin. Melanin particles were used to immunize BALB/c mice in order to produce a total of five anti-melanin monoclonal antibodies (mAbs). The latter mAbs were strongly reactive both with intact conidia and with extracted melanin particles by ELISA and immunofluorescence reactivity. Immunofluorescence labelling with the novel mAbs was used to examine the temporal expression of melanin during in vitro culture of A. fumigatus--melanization was confined to conidial structures and was absent from hyphae. SDS-PAGE L-3,4-dihydroxyphenylalanine (L-DOPA) substrate analysis confirmed the presence of a laccase-type activity in conidial extracts, but not in hyphae. Melanin-binding mAbs were used to detect the presence of melanized conidia in three patients with nasal aspergilloma, indicating that in vivo melanization may occur during infection.

Travel-associated skin disease.

Travel associated skin disease is extremely common and a frequent cause of the returning traveller seeking medical attention. Widespread cutaneous eruptions usually represent reactive rashes, indicating an underlying systemic infection or allergic reaction. Patients with disseminated or spreading rashes following travel often present with fever and malaise. In contrast, those presenting with localised skin disease such as a blister, nodule, plaque, ulcer etc are usually well in themselves but have sustained a bite/sting/penetrating injury or introduction of infection directly into the skin at the affected site. As a general rule widespread rashes are investigated with blood tests/serology and localised lesions with a skin biopsy for culture and histology.

Skin disease among human immunodeficiency virus-infected adolescents in Zimbabwe: a strong indicator of underlying HIV infection.

BACKGROUND: Southern Africa is witnessing the emergence of an epidemic of long-term survivors of vertically acquired human immunodeficiency virus (HIV) infection presenting with untreated HIV as adolescents. Dermatologic conditions, common in both HIV-infected adults and children, have not been described in this age-group. We investigated the prevalence and spectrum of skin conditions in adolescents admitted to hospitals in Zimbabwe. METHODS: A total of 301 consecutive adolescents admitted to 2 central Harare hospitals, underwent a dermatologic examination. Clinical history, HIV serology, and CD4 lymphocyte counts were obtained. Herpes simplex virus-2 serology was used as a surrogate marker for sexual activity. RESULTS: : A total of 139 (46%) patients were HIV-1 antibody positive, of whom only 2 (1.4%) were herpes simplex virus-2 antibody positive. The prevalence of any skin complaint among HIV-infected and uninfected participants was 88% and 14%, respectively (odds ratio: 37.7, 95% confidence interval: 19.4-72). The most common HIV-related conditions were pruritic papular eruptions (42%) and plane warts >5% of body area (24%). Having 3 or more skin conditions, a history of recurrent skin rashes and angular cheilitis were each associated with CD4 counts <200 cells/microL (P < 0.03, P < 0.01, and P < 0.05, respectively). CONCLUSIONS: Skin disease was a common and striking feature of underlying HIV-infection in hospitalized HIV-infected adolescents in Zimbabwe. In resource-poor settings with maturing epidemics, the presence of skin disease should be regarded as a strong indication for HIV testing and especially as it may reflect advanced immunosuppression. The high frequency of multiple plane warts has not previously been described, and may be a feature that distinguishes vertically-infected from horizontally-infected adolescents.

Synthesis of melanin pigment by Candida albicans in vitro and during infection.

Melanins are implicated in the pathogenesis of several important human diseases. This study confirmed the presence of melanin particles in Candida albicans in vitro and during infection. Dark particles were isolated from the digestion of C. albicans cultures and from infected tissue, as established by electron microscopy and immunofluorescence techniques.

Synthesis of melanin-like pigments by Sporothrix schenckii in vitro and during mammalian infection.

Melanin has been implicated in the pathogenesis of several important human fungal pathogens. Existing data suggest that the conidia of the dimorphic fungal pathogen Sporothrix schenckii produce melanin or melanin-like compounds; in this study we aimed to confirm this suggestion and to demonstrate in vitro and in vivo production of melanin by yeast cells. S. schenckii grown on Mycosel agar produced visibly pigmented conidia, although yeast cells grown in brain heart infusion and minimal medium broth appeared to be nonpigmented macroscopically. However, treatment of both conidia and yeast cells with proteolytic enzymes, denaturant, and concentrated hot acid yielded dark particles similar in shape and size to the corresponding propagules, which were stable free radicals consistent with identification as melanins. Melanin particles extracted from S. schenckii yeast cells were used to produce a panel of murine monoclonal antibodies (MAbs) which labeled pigmented conidia, yeast cells, and the isolated particles. Tissue from hamster testicles infected with S. schenckii contained fungal cells that were labeled by melanin-binding MAbs, and digestion of infected hamster tissue yielded dark particles that were also reactive. Additionally, sera from humans with sporotrichosis contained antibodies that bound melanin particles. These findings indicate that S. schenckii conidia and yeast cells can produce melanin or melanin-like compounds in vitro and that yeast cells can synthesize pigment in vivo. Since melanin is an important virulence factor in other pathogenic fungi, this pigment may have a similar role in the pathogenesis of sporotrichosis.