Alitretinoin abrogates innate inflammation in palmoplantar pustular psoriasis.

BACKGROUND: Palmoplantar pustular psoriasis is often recalcitrant to therapy. Here we evaluated the therapeutic effect of alitretinoin in patients with recalcitrant palmoplantar pustular psoriasis and investigated subsequent immunopathological alterations. METHODS: Seven patients with palmoplantar pustular psoriasis were treated with oral alitretinoin 30 mg once daily for 12 weeks. Efficacy was assessed by palmoplantar pustular psoriasis area and severity index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus and an overall patient assessment. Immunohistochemical staining for neutrophil elastase, CD3, CD4, CD8, CD1a CD11c, CD303,CD68, CD69, CD208 and HLA-DR was on lesional skin biopsies obtained before and after 12 weeks of treatment. RESULTS: PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of treatment with alitretinoin. The overall patient assessment ranged from 60% to 90% clinical improvement. In correlation with clinical improvement a significant reduction, particularly of neutrophils, macrophages and dendritic cells, was also observed in the skin sections. Alitretinoin was well tolerated except for headache during the first month of treatment in two patients. Limitations of the study are a missing control group and the concomitant usage of topical therapy. DISCUSSION: Our findings suggest that alitretinoin may represent a new and promising therapy for recalcitrant palmo-plantar psoriasis and warrants further controlled studies to confirm efficacy and safety of alitretinoin in this disease.

Oral mucosal morphea: a new variant.

Morphea is a cutaneous disorder characterized by an excessive collagen deposition. While in almost all cases the sclerosing process exclusively affects the skin, there are anecdotal cases in which associated mucosal involvement has been described. We here report the case of a woman developing a whitish indurated plaque over the left upper vestibular mucosa and hard palate leading to dental mobility and exposure of the roots of several teeth. Cone beam computed tomography of the left maxilla showed bone resorption involving the upper cuspid to the second molar region with widened periodontal ligament spaces, while light microscopy studies demonstrated epithelial atrophy and fibrosis of the dermis extending into the submucosa with hyalinization of subepithelial collagen. Our observation expands the spectrum of clinical presentations of morphea and provides the first example of isolated oral morphea. Its recognition is important to avoid significant local complications.

NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions.

BACKGROUND: The spectrum of cutaneous adverse drug reactions (cADRs) ranges from benign presentations to severe life-threatening forms such as toxic epidermal necrolysis (TEN). In TEN, granulysin has been shown to be the key cytotoxic molecule. Still, little is known about the expression of granulysin in other cADRs. As an important source of granulysin, natural killer (NK) cells are of major interest in cADRs. Recently, NKp46 has been identified as the most selective NK-cell marker. However, the role of NKp46(+) cells in cADRs and their contribution to granulysin expression remain to be elucidated. METHODS: Immunohistochemical and immunofluorescence staining of tissue sections from multiple cADRs were quantitatively and qualitatively evaluated. Further, in vivo and in vitro drug-stimulation tests were performed. RESULTS: Granulysin is expressed at different levels in multiple cADRs both by NKp46(+) cells and by CD8(+) T cells. Even in mild forms of cADRs, granulysin can be induced in vivo and in vitro in a drug-specific manner. NKp46(+) cells were found to infiltrate the dermal/epidermal junction particularly in TEN. CONCLUSION: The impressive clinical differences of cADRs may not be uniquely explained by the expression of granulysin. Additional factors such as drug-specific activation and recruitment of NKp46(+) cells to the epidermis may play a role in determining the severity of cADRs. Therefore, unraveling the effects of drugs on NK-cell activation and trafficking may help to better understand the cytotoxic mechanisms behind cADRs.

Nail Lichen Planus: Successful Treatment with Etanercept.

BACKGROUND: Etanercept is a fully human tumor necrosis factor a receptor fusion protein that binds tumor necrosis factor a with greater affinity than natural receptors. Biologics are widely used in the treatment of psoriasis and psoriasis arthritis and may represent a new therapeutic option for some patients with psoriatic nail disease. CASE REPORT: We report a case of lichen planus limited to the toe nails successfully treated with etanercept monotherapy. CONCLUSION: The significant improvement of our case suggests that etanercept is an effective treatment modality for lichen planus limited particularly to the nails. Further controlled studies are needed to establish the effectiveness and therapeutic regimes.

Marked improvement in nail psoriasis during treatment with adalimumab.

BACKGROUND: Nail involvement is known as a common finding in psoriatic patients and represents a significant impact on patients' quality of life. The treatment of nail psoriasis is often challenging, and there is a need for new therapeutic options. Biologicals effective in the treatment of moderate to severe chronic plaque psoriasis may represent a new therapeutic modality for this disease. Adalimumab is a fully human IgG1 monoclonal antibody that binds to tumor necrosis factor alpha with high affinity and specificity. OBSERVATIONS: We report two cases of rapid improvement in nail psoriasis under adalimumab monotherapy with maintained effectiveness despite intermittent treatment as well as long remission after therapy discontinuation. CONCLUSION: The marked improvement of our two cases indicates that adalimumab may also help ameliorate nail psoriasis and warrants further controlled studies to establish the effectiveness and therapeutic regimes.