Tuberculous cellulitis: diseases behind cellulitislike erythema.

An 89-year-old man presented with an inflammatory erythematous plaque on the left thigh that closely mimicked cellulitis. Empiric therapies with ordinary antibiotics were not effective. A skin biopsy showed epithelioid cell granulomas throughout the dermis and subcutis. Ziehl-Neelsen stain revealed numerous acid-fast bacilli. Additionally, Mycobacterium tuberculosis was isolated from a skin biopsy specimen as well as gastric fluid and sputum cultures. He was diagnosed with tuberculous cellulitis with pulmonary tuberculosis. Cellulitis is a common disease seen by dermatologists; however, sometimes other diseases may masquerade as this banal illness. Among them, cutaneous tuberculosis should be excluded because of its clinical significance. Most cases of cutaneous tuberculosis are symptom free, but tuberculous cellulitis is sometimes painful. Therefore, cutaneous tuberculosis should always be considered in the differential diagnosis of a cellulitislike rash if the lesions do not respond to ordinary antibiotic therapy, especially in countries with a high incidence of tuberculosis.

A case of type IV solar urticaria identified by reverse in vitro serum test.

We had a 17-year-old male patient with solar urticaria diagnosed as type IV of modified Harber's classification. The action spectrum of this case was estimated to be 433-499 nm and the inhibition spectrum was 533 nm. Both in vitro serum test and tentatively designated "reverse in vitro serum test" were positive. The patient was prescribed 20 mg/day epinastine hydrochloride (Alesion) orally for 49 weeks with improvement of the symptoms.

Mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors sensitize reduced glucocorticoid response mediated by TNFalpha in human epidermal keratinocytes (HaCaT).

Glucocorticoids (GCs) are essential drugs administered topically or systematically for the treatment of autoimmune skin diseases such as pemphigus. However, a certain proportion of patients does not respond well to GCs. Although studies on the relationship between cytokines and GC insensitivity in local tissues have attracted attention recently, little is known about the underlying mechanism(s) for GC insensitivity in epidermal keratinocytes. Here, we report that tumor necrosis factor (TNF) alpha reduces GC-induced transactivation of endogenous genes as well as a reporter plasmid which contains GC responsive element (GRE) in human epidermal keratinocyte cells (HaCaT). The GC insensitivity by TNFalpha was not accompanied by changes in mRNA expressions of GR isoforms (alpha or beta). However, we observed that mitogen-activated protein kinase kinase-1/extracellular signal-regulated kinase (MEK-1/ERK) inhibitors (PD98059 and U0126) significantly sensitized the GC-induced transactivation of anti-inflammatory genes (glucocorticoid-induced leucine zipper (GILZ) and mitogen-activated protein kinase phosphatase (MKP)-1) and FK506 binding protein (FKBP) 51 gene in the presence of TNFalpha. Additionally, we observed that TNFalpha reduced prednisolone (PSL)-dependent nuclear translocation of GR, which was restored by pre-treatment of MEK-1 inhibitors. This is the first study demonstrating a role of the MEK-1/ERK cascade in TNFalpha-mediated GC insensitivity. Our data suggest that overexpression of TNFalpha leads to topical GC insensitivity by reducing GR nuclear translocation in keratinocytes, and our findings also suggest that inhibiting the MEK-1/ERK cascade may offer a therapeutic potential for increasing GC efficacy in epidermis where sufficient inflammatory suppression is required.

Delayed-type hypersensitivity reaction to paraphenylenediamine is mediated by 2 different pathways of antigen recognition by specific alphabeta human T-cell clones.

BACKGROUND: Allergic contact dermatitis to paraphenylenediamine (PPD) is a frequent cause of morbidity and occupational disability. OBJECTIVE: The aim of the study was to characterize T-cell responses to PPD and Bandrowski's base (BB), an autoxidation product of PPD, by using polyclonal and monoclonal T-lymphocyte cultures. METHODS: PPD- and BB-driven proliferation of PBMCs and T-cell clones (TCCs) was assessed by means of tritiated thymidine incorporation. Surface markers were studied by means of flow cytometry, and cytokine generation was assessed with an ELISA. RESULTS: TCCs, with one exception, were CD4+/CD45RO+, and T-cell receptors were alphabeta+. Three of 6 TCCs expressed Vbeta 16. TCC stimulation was HLA-DP restricted, and TCCs secreted IL-4, IL-5, and marginal levels of IFN-gamma. TCCs reacted to both PPD and BB. Presentation of BB to TCCs was dependent on viable antigen-presenting cells (APCs) pulsed for 4 hours, and fixed APCs failed to stimulate TCCs. Moreover, polyclonal responses to BB were enhanced by metabolically active enzymes, such as cytochrome P450 enzymes. BB has to be metabolized and processed. In contrast, fixation of APCs did not impair their ability to present PPD to TCC, whereas pulsing of APCs with PPD failed to stimulate TCCs. Thus PPD had to be present during the process, and polyclonal stimulation was not enhanced by cytochromes. CONCLUSION: These results suggest that PPD itself can be recognized by T cells through a processing-independent pathway, whereas its autoxidation product, BB, required processing and possibly metabolism to stimulate the same TCC. Our data demonstrate that 2 distinct pathways of antigen presentation to activate specific TCCs are involved in the immune response to PPD.