Immunohistochemical markers for histopathological diagnosis and differentiation of acute cutaneous graft-versus-host disease.

Graft-versus-host disease (GvHD) is a major complication following stem-cell or solid-organ transplantation. Accurate diagnosis of cutaneous GvHD is challenging, given that drug eruptions and viral rashes may present with similar clinical/histological manifestations. Specific markers are not available. We performed the histological examination of biopsy samples from acute GvHD (aGvHD; n = 54), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; n = 27), maculopapular drug eruption (MDE; n = 26) and healthy controls (n = 26). Samples of aGvHD showed a decrease in Langerhans cells (LC, p = 0.0001) and an increase in macrophages (MΦ, p = 0.0001) compared to healthy skin. Compared to SJS/TEN, MDE and healthy skin, aGvHD biopsies contained greater numbers of CD4+ and CD8+ T cells. The majority of CD4+ T-helper cells were localized in the upper dermis, whereas cytotoxic CD8+ T cells were found in the epidermis. Increased numbers of CD56+ natural killer (NK) cells in the upper dermis of aGvHD skin (p = 0.007) were not observed in controls or SJS/TEN and MDE. There were no differences in elafin staining between aGvHD and the latter two conditions. Acute GvHD appears to have a distinct inflammatory cell profile (T cells/NK cells) that may aid establishing in a more accurate diagnosis, especially when used to rule out differential diagnoses such as SJS/TEN or MDE.

Cicatricial pemphigoid (mucous membrane pemphigoid): current and emerging therapeutic approaches.

The treatment of cicatricial pemphigoid, also called mucous membrane pemphigoid (MMP), poses a great challenge, because the condition often takes an intransigent course despite all therapeutic efforts. Because of its diverse clinical manifestations, patients with MMP often have to be treated by a variety of specialists, including dermatologists, ophthalmologists, ear, nose, and throat specialists, and dentists. Since there are almost no randomized, controlled, double-blind studies comparing the use of various therapeutic agents in this condition, treatment decisions still rely heavily on individual clinicians' experience. Many different therapeutic regimens have been described in the literature, but only a few seem to hold up as valid alternatives. Systemic corticosteroids are still the agent of first choice, especially as rescue medication, for curtailing acute exacerbations. However, because of their well known long-term adverse effects, corticosteroids must be combined with immunosuppressive and/or anti-inflammatory agents. To determine which drug to choose, it is helpful to categorize patients -- as recommended by the First International Consensus -- in terms of high- and low-risk depending on the site and severity of their disease and on how rapidly it progresses. The recommended treatment for high-risk patients (i.e. patients with ocular, genital, laryngeal, esophageal or nasopharyngeal involvement) is a combination of prednisone and cyclophosphamide, or alternatively azathioprine. Once clinical improvement is evident, the corticosteroids should be slowly tapered. Dapsone is another alternative that may be used in high-risk patients, but patients who do not show any short-term improvement on this regimen should be switched to cyclophosphamide. Intravenous immunoglobulins are another effective, but expensive, treatment option in high-risk patients. Low-risk patients may well be managed with topical therapy alone, such as corticosteroids or cyclosporine. Other systemic options include dapsone, tetracycline, and nicotinamide as well as azathioprine in combination with low doses of corticosteroids. Various other systemic and topical agents, and recently biologics such as etanercept, have been reported to be effective in the treatment of MMP. However, most of the reported cases consisted of only small patient numbers and the true benefit of such agents in the condition is therefore not yet clear.

Increased expression of VEGF in glomeruloid reactive angioendotheliomatosis.

Reactive angioendotheliomatosis (RAE) is a very rare disorder characterized by marked proliferation of endothelial cells. It is often associated with infections, such as subacute bacterial endocarditis, but has also been described as an early sign of a developing hematological malignancy. We report the case of a 71-year-old Caucasian female who developed lupus-like RAE lesions. A thorough diagnostic workup and subsequent 3-year clinical follow-up revealed no sign of an underlying infectious or neoplastic disorder. Repetitive serum immunofixations were only once consistent with a monoclonal gammopathy of undetermined significance. In lesional skin, the pronounced bud-like endothelial cell formation was associated with an increased epidermal expression of vascular endothelial growth factor (VEGF), a potent angiogenic mediator. In accordance with the paracrine action of epidermally derived VEGF, vascular endothelial cells in lesional skin revealed increased expression of the VEGF receptor VEGFR-2 (KDR). This case suggests a possible role of epidermally derived VEGF in endothelial cell proliferation in RAE.

Treatment of recalcitrant cicatricial pemphigoid with the tumor necrosis factor alpha antagonist etanercept.

The treatment of cicatricial pemphigoid is generally regarded as difficult and usually relies on individual clinical experience. Corticosteroids, as drugs of first choice, often have to be combined with steroid-sparing agents to prevent hazardous, long-term side effects. We describe a 72-year-old woman with long-standing cicatricial pemphigoid recalcitrant to established treatment regimens who responded rapidly and lastingly to therapy with the tumor necrosis factor alpha antagonist etanercept. To our knowledge, this is the first report of its use in the treatment of a bullous autoimmune disease.