Simone Garcovich

IL-17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes

Th17 is a newly identified lineage of effector T cells involved in autoimmunity and immune responses to pathogens. We demonstrate in this study the pathogenic role of IL-17–producing CD4+ T lymphocytes in allergic contact dermatitis (ACD) to skin-applied chemicals. IL-17+ T cells infiltrate ACD reactions and predominantly distribute at the site of heavy spongiosis. Skin IL-17+ T cells were functionally and phenotypically heterogeneous: although pure Th17 prevailed in ACD skin, hapten responsiveness was restricted to Th1/IL-17 (IFN-γ+IL-17+) and Th0/IL-17 (IFN-γ+IL-17+IL-4+) fractions, and to lesser extent Th2/IL-17 cells. In the IFN-γ–dominated ACD environment, IL-17–releasing T cells affect immune function of keratinocytes by promoting CXCL8, IL-6, and HBD-2 production. In addition, compared with Th1, supernatants from Th1/IL-17 T cells were much more efficient in inducing ICAM-1 expression on keratinocytes and keratinocyte–T cell adhesiveness in vitro. As a consequence, exposure to combined IFN-γ and IL-17 rendered keratinocytes susceptible to ICAM-1–dependent Ag nonspecific T cell killing. Thus, IL-17 efficiently amplifies the allergic reaction by rendering virtually all of the T lymphocytes recruited at the site of skin inflammation capable to directly contribute to tissue damage.

The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial

Platelet‐rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, we report the results of a randomized, evaluator‐blinded, placebo‐controlled, half‐head group study to compare, with the aid of computerized trichograms, hair regrowth with PRP versus placebo. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. PRP, prepared from a small volume of blood, was injected on half of the selected patients scalps with pattern hair loss. The other half was treated with placebo. Three treatments were administered to each patient at 30‐day intervals. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki67 evaluation. Patients were followed for 2 years. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 33.6 hairs in the target area, and a mean increase in total hair density of 45.9 hairs per cm2 compared with baseline values. No side effects were noted during treatment. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles 2 weeks after the last PRP treatment compared with baseline value (p < .05). We also observed an increase of Ki67+ keratinocytes in the epidermis and of hair follicular bulge cells, and a slight increase of small blood vessels around hair follicles in the treated skin compared with baseline (p < .05). Relapse of androgenic alopecia was not evaluated in all patients until 12 months after the last treatment. After 12 months, 4 patients reported progressive hair loss; this was more evident 16 months after the last treatment. Those four patients were re‐treated. Our data clearly highlight the positive effects of PRP injections on male pattern hair loss and absence of major side effects. PRP may serve as a safe and effective treatment option against hair loss; more extensive controlled studies are needed.

The Effect of Autologous Activated Platelet Rich Plasma (AA-PRP) Injection on Pattern Hair Loss: Clinical and Histomorphometric Evaluation

To investigate the safety and clinical efficacy of AA-PRP injections for pattern hair loss. AA-PRP, prepared from a small volume of blood, was injected on half of the selected patients scalps with pattern hair loss. The other half was treated with placebo. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair re-growth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. At the end of the 3 cycles of treatment, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 18.0 hairs in the target area, and a mean increase in total hair density of 27.7 ( number of hairs/cm2) compared with baseline values. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles two weeks after the last AA-PRP treatment compared to baseline value (P < 0.05). We also observed an increase of Ki67+ keratinocytes of epidermis and of hair follicular bulge cells and a slight increase of small blood vessels around hair follicles in the treated skin compared to baseline (P < 0.05).

Clinical applicability of Quantiferon-TB-Gold testing in psoriasis patients during long-term anti-TNF-alpha treatment: a prospective, observational study

Backgroundu2002 Psoriasis patients who are treated with tumour necrosis factor (TNF)‐alpha antagonists are at increased risk of reactivation of latent tuberculosis infection (LTBI) and should be adequately screened and monitored during active treatment.

Treatment of refractory adult-onset pityriasis rubra pilaris with TNF-alpha antagonists: A case series

Backgroundu2002 Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents.

Long-Term Treatment of Severe SAPHO Syndrome with Adalimumab

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome defines an association of inflammatory cutaneous disorders with osteoarticular manifestations and represents a clinical and therapeutic challenge. We report a case of severe SAPHO syndrome with acne conglobata and a diffuse involvement of the anterior chest wall and sacroiliac joints that required treatment with isotretinoin and adalimumab, a new fully human anti-tumor necrosis factor (TNF)-α monoclonal antibody. Combination treatment determined a complete clinical remission of cutaneous and osteoarticular manifestations after 48 weeks. Despite maintenance of clinical remission, follow-up imaging studies after 24 months of adalimumab monotherapy revealed osteoarticular disease progression, with features of inflammatory osteitis.TNFα antagonists have been used as third-line therapy for SAPHO syndrome in single case reports or case series, but these lack consistent long-term follow-up. SAPHO syndrome can present an intermittentfavorable course in the majority of cases as well as a chronic-progressive course, the latter requiring aggressive combination treatment with TNFα antagonists and conventional systemic agents.

An unusual variant of granulomatous adnexotropic cutaneous T‐cell lymphoma

SIR, A 40-year-old man reported the slow progressive appearance, during the previous 6 years, of pruritic erythematous lesions on the trunk, buttock, abdomen, axilla, genital area and forearm (Fig. 1a). Lesions consisted of follicular papules, comedones, milia and cysts. Lesional areas were alopecic (Fig. 1b), and diffuse alopecia was also present on the scalp and beard area, along with comedones and cysts. The patient reported severe skin dryness, especially in the involved areas. No impairment of salivary or lacrimary function was noted. Serological and haematological tests were all normal or negative. Because of the diffuse presence of cysts and comedones, a diagnosis of chloracne had been made in another institution; the clinical diagnosis was confirmed histologically by the presence of infundibular cysts and a granulomatous foreign body reaction to keratin scales. A further biopsy was performed: the most striking histological feature was a lymphocytic infiltrate involving eccrine glands and coils along with a characteristic epithelial hyperplasia (Figs 1c,d). This picture fits perfectly with that reported in the literature as being characteristic of syringolymphoid hyperplasia, also known as syringotropic mycosis fungoides or syringotropic cutaneous T-cell lymphoma (CTCL). The hair follicles were involved by the lymphocytic infiltrate in a manner similar to that of the eccrine glands. Follicles were surrounded by a dense lymphocytic infiltrate, with extensive exocytosis. Occasional Pautrier microabscesses were evident in the follicular sheath. This pattern is that of pilotropic mycosis fungoides, a form of folliculotropic CTCL. Many follicles were entirely trans-

Onset of lichen planopilaris during treatment with etanercept.

1 EMEA Committee for Proprietary Medicinal Products (CPMP). Note for Guidance on Clinical Investigation of Medicinal Products Indicated for the Treatment of Psoriasis. CPMP ⁄EWP ⁄2454 ⁄02. London: EMEA, 2004. 2 LABAG. Landelijk beoordelingsinstituut voor aanvragen groeihormoon en biologicals voor reumatologische en dermatologische indicaties. Home page at http://www.labag.nl/ (last accessed 13 January 2008). 3 Nijsten T, Lambert J. Dermatologists’ views and opinions about photo(chemo)therapy and conventional systemic psoriasis therapies: results from a Belgian survey. Dermatology 2006; 213:123–33. 4 Nijsten TE, Stern RS. The increased risk of skin cancer is persistent after discontinuation of psoralen + ultraviolet A: a cohort study. J Invest Dermatol 2003; 121:252–8. 5 Lim JL, Stern RS. High levels of ultraviolet B exposure increase the risk of non-melanoma skin cancer in psoralen and ultraviolet Atreated patients. J Invest Dermatol 2005; 124:505–13. 6 Marcil I, Stern RS. Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested cohort crossover study. Lancet 2001; 358:1042–5. 7 Paul CF, Ho VC, McGeown C et al. Risk of malignancies in psoriasis patients treated with cyclosporine: a 5 y cohort study. J Invest Dermatol 2003; 120:211–16.

Lichenoid red tattoo reaction: histological and immunological perspectives

As tattooing practices increase, delayed-type inflammatory reactions represent an uncommon adverse event to tattoo pigments. Different reaction patterns, such as eczematous, lichenoid, granulomatous and pseudolymphomatous reactions, have been previously reported, especially in association with metals contained in red tattoo pigments. We report a lichenoid papular reaction to an organic red tattoo ink, characterized by an intense mononuclear infiltrate dominated by CD8(+) T cells and CD56(+) lymphocytes and distributed in the superficial dermis around the red pigment and in the epidermis. Cytofluorimetric analysis of the lesional skin infiltrate confirmed the high frequency of cytotoxic CD8(+ )T cells and CD56(+)CD16(-) lymphocytes, most of which release type 1 cytokines. Chemical analysis of the red tattoo pigment confirmed its organic nature and the presence of intermediate reactive compounds. The lichenoid tissue reaction to red organic tattoo pigment showed the prototypical features of a cytotoxic inflammatory response to foreign substances (xenobiotics). The chemically unstable and reactive nature of modern tattoo pigments has to be taken into account by the clinician as well by the tattoo recipients.

CD56 highCD16 - NK cell involvement in cutaneous lichen planus.

Lichen planus is an inflammatory disease of the skin and mucous membranes characterized by vacuolization of basal keratinocytes associated with a prominent junctional lymphocyte infiltrate which comprises Txa0lymphocytes, NK cells, myeloid and plasmacytoid dendritic cells. Basal keratinocyte damage is considered as being a consequence of a lymphocytic cytotoxic attack, mostly mediated by perforin+CD8+ Txa0lymphocytes. NK cells have been described to infiltrate inflamed skin and significantly contribute to the amplification of immune-mediated skin diseases, thanks to their cytotoxic activity and the release of pro-inflammatory cytokines. Here, we investigated the characteristics and functional properties of NK lymphocytes involved in lichen planus. Double staining immunohistochemistry showed a considerable number (6.42 ± 2.2% of the total cellular infiltrate) of CD3-CD56+ cells in early lichen planus lesions, mostly distributed in the papillary dermis and at the epidermal-dermal interface. Skin NK cells isolated from lichen planus lesions belong to the CD56highCD16- subset, are highly positive for perforin and natural cytotoxic receptors NKG2D and NKp44, and, in accordance with their phenotype, are negative for KIRs receptors CD158a and CD158b. Skin CD56highCD16- NK cells display a CCR6+CXCR3+CCR5+ChemR23+ chemokine receptor asset for homing into inflamed skin. In terms of cytokine release, skin CD56highCD16- NK cells are able to secrete IFN-γ, TNF-α and hardly release IL-22, IL-17 and IL-4. Overall, our data propose a pro-inflammatory role of NK lymphocytes in lichen planus.