Paolo Romanelli

Evaluation of the Efficacy of Acitretin Therapy for Nail Psoriasis

OBJECTIVE To evaluate the therapeutic efficacy of acitretin in patients with isolated nail psoriasis. DESIGN Open study involving 36 patients with moderate to severe nail psoriasis treated with acitretin. SETTING University-based outpatient dermatology clinic specializing in nail diseases. PATIENTS A total of 27 men and 9 women (mean age, 41 years) with nail psoriasis. INTERVENTION Therapy consisted of acitretin, 0.2 to 0.3 mg/kg/d, for 6 months. MAIN OUTCOME MEASURES Clinical evaluation, and Nail Psoriasis Severity Index (NAPSI) and modified NAPSI scores before therapy, every 2 months during therapy, and 6 months after treatment. RESULTS The mean percentage of reduction of the NAPSI score after treatment was 41%; the mean percentage of reduction of the modified NAPSI score of the target nail was 50%. Clinical evaluation at 6 months showed complete or almost complete clearing of the nail lesions in 9 patients (25%), moderate improvement in 9 (25%), mild improvement in 12 (33%), and no improvement in 6 (11%). CONCLUSION Results from low-dose acitretin therapy show NAPSI score reductions comparable with those studies evaluating biologic drugs for nail psoriasis and suggest that low-dose systemic acitretin should be considered in the treatment of nail psoriasis.

Hair casts are a dermoscopic clue for the diagnosis of traction alopecia.

FCAS was infiltrated with IL-17-positive cells, which appeared to be neutrophils. This is the first report of IL-17 expression in an urticarial lesion of a patient with FCAS. In conclusion, we hypothesize that the urticarial rash in FCAS is induced by IL-1b as a result of NLRP3 activation; IL-1b activates Th17 cells leading to IL-17-associated neutrophil recruitment into the dermis. In addition, the neutrophil infiltrate might secrete more IL-17, and cause further inflammation. The blockage of IL-1b by anakinra provides therapeutic benefit for patients with CAPS; however, long-term benefit and safety data are needed. We speculate that IL-17 might be a potential therapeutic target.

Permanent alopecia after systemic chemotherapy: A clinicopathological study of 10 cases

Anagen effluvium due to chemotherapy is usually reversible with complete hair regrowth. However, there is increased evidence that certain chemotherapy regimens can cause dose-dependent permanent alopecia. The histological features of this type of alopecia and the mechanisms of its origin are not known yet. We discuss the histological features of 10 cases of permanent alopecia after systematic chemotherapy with taxanes (docetaxel) for breast cancer (6 patients), busulfan for acute myelogenous leukemia (3 patients), and cisplatin and etoposide for lung cancer (1 patient). All patients had moderate to very severe hair thinning, which in 4 cases was more accentuated on androgen-dependent scalp regions. Patients complained that scalp hair did not grow longer than 10 cm and showed altered texture. Paired scalp biopsies from the affected scalp areas were obtained and evaluated in serial horizontal and vertical sections. The histology of all specimens was characterized by a nonscarring pattern with a preserved number of follicular units and lack of fibrosis. The hair count revealed decreased number of terminal hairs, increased telogen hairs, and increased miniaturized vellus-like hairs with a terminal to vellus and anagen to telogen ratios of 1:1 and 3.6:1, respectively. There was increased number of fibrous streamers (stelae) in both reticular dermis and subcutis. Arao-Perkins bodies were found in the subcutaneous portions of the streamers. The histological findings of permanent alopecia after chemotherapy are those of a nonscarring alopecia similar to androgenetic alopecia. Dermatopathologists should be aware of this condition as the absence of fibrosis and the presence of miniaturized hairs may be considered as features consistent with a diagnosis of androgenetic alopecia. Hence, these cases could easily be misdiagnosed in the absence of a good clinicopathological correlation.

Tumor necrosis factor–alfa in nonhealing venous leg ulcers

BACKGROUND Venous leg ulcers are responsible for more than half of all lower extremity ulcerations, affecting more than one million Americans annually. Studies have demonstrated alterations in levels of proinflammatory cytokines in patients with chronic wounds, including tumor necrosis factor-alfa (TNFalpha), which may be implicated in wound chronicity. OBJECTIVE To test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNFalpha as compared to normal skin. METHODS Five patients with nonhealing healing chronic venous leg ulcers were recruited. Two 4-mm punch biopsy specimens were obtained: one from the wound margin and one from noninvolved, non-sun exposed normal skin on the flexor aspect of the forearm. Tissue samples were processed using fixed with formalin stained by immunohistochemistry for TNFalpha. Qualitative and quantitative comparisons were made for the presence of TNFalpha receptor in all tissue samples, specifically comparing the presence of TNFalpha in nonhealing venous leg ulcer samples versus normal skin. RESULTS The overall staining score for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNFalpha was significantly less in the two nonhealing venous leg ulcers that were present for the shortest duration compared to the other ulcers of longer duration (P = .048). LIMITATIONS The small sample size may mitigate the clinical implications of findings. CONCLUSIONS Increased levels of TNFalpha in nonhealing venous leg ulcers, especially those of longer duration, implies that excessive inflammation may be causal in wound chronicity and suggests potential therapeutic alternatives.

Pseudoxanthoma elasticum–like papillary dermal elastolysis: A large case series with clinicopathological correlation

BACKGROUND Pseudoxanthoma elasticum (PXE)-like papillary dermal elastolysis (PDE) is a rare acquired elastic tissue disorder. To date, less than 20 cases have been reported. OBJECTIVE We report a case series of 17 patients presenting with PXE-like PDE and discuss the clinicopathological correlation. METHODS Seventeen cases of PXE-like PDE were collected prospectively and evaluated for common demographic, clinical, and histopathological features. RESULTS All patients were women with a mean age of 61.8 years. The lateral sides and back of neck were the most common sites of involvement (100%), followed by the supraclavicular region (41.2%) and the axilla (35.3%). Systemic involvement was absent in all cases, and in 7 patients the discovery of PXE-like PDE was an incidental finding. The main histopathologic features included complete loss (82.4%) or marked reduction (17.6%) of elastic fibers in the papillary dermis and the presence of melanophages in the same zone (88.2%). LIMITATIONS Our results require validation with a larger series. CONCLUSIONS Our findings help to differentiate PXE-like PDE from similar elastic tissue disorders based on the selective elastic tissue elimination in the papillary dermis and the presence of melanophages in the same zone as a possible consequence of subclinical junctional photodamage. PXE-like PDE is likely underdiagnosed rather than rare, and dermatologists should be aware of its similarity to inherited PXE to spare unnecessary investigations because of the lack of systemic involvement. Clinicopathologic correlation is critical as hematoxylin-eosin staining is nonspecific and elastic tissue stains are necessary to make the correct diagnosis.

Tumor necrosis factor-α in vitiligo: direct correlation between tissue levels and clinical parameters.

Background: Experimental evidences have shown that tumor necrosis factor (TNF)-α may play a role in the pathogenesis of nonsegmental vitiligo, and successful cases of vitiligo treated with TNF-α inhibitors have been recently reported. Materials and methods: Two cases of refractory generalized vitiligo, which showed high tissue levels of TNF-α, were commenced anti-TNF-α antibody etanercept 50 mg weekly. A retrospective study, considering chart review and immunohistochemical staining for TNF-α, was then carried out on eight additional patients affected by untreated vitiligo. Results: Etanercept achieved improvement of vitiligo in two patients at 6-month follow-up. Five out of eight specimens showed a strong cytoplasmic staining for TNF-α. Considering all 10 cases, patients with a strong TNF-α staining were characterized by a higher vitiligo disease activity score than patients with a weak staining. Discussion: These findings, albeit limited in significance by the low number of cases and the retrospective nature of the study, confirm a probable role of TNF-α in the pathogenesis of vitiligo. The intensity of TNF-α staining in vitiligo lesions may be worth to be further studied as a biomarker for potentially successful anti-TNF-α treatment of nonsegmental vitiligo in cases refractory to conventional treatment.

Papuloerythroderma 2009: Two New Cases and Systematic Review of the Worldwide Literature 25 Years after Its Identification by Ofuji et al.

Background: Even after the description of papuloerythroderma of Ofuji (PEO) in 1984, little is known about this clinical entity. Objective:To report on 2 new cases of PEO and review of the worldwide literature on this topic. Methods: Article citations were searched on several biomedical search engines (PubMed, EMBASE, SCOPUS, Google Scholar). Papers were retrieved either online or in print. Results: A grand total of 170 PEO cases were identified. Most patients were older than 55 years and of Asian or white descent, with an overall male/female ratio of 4.0. Itch and the deck-chair sign were observed in all patients. Peripheral eosinophilia, lymphocytopenia and increased serum IgE were common findings. Histopathology mostly showed aspecific inflammation, while 17 showed histological features of cutaneous T-cell lymphoma (CTCL). Atopy, malignancies, infections and drugs were rarely linked to PEO. Conclusion: PEO represents a rather monomorphous entity both clinically and, with the remarkable exception of CTCL, also histologically. Nonetheless, no causative factor could be identified in the vast majority of cases. An etiological classification and diagnostic criteria are proposed in the attempt to contribute framing this puzzling clinical entity.

A rare case of a cutaneous squamomelanocytic tumor: revisiting the histogenesis of combined neoplasms.

We describe what we believe to be the seventh report of a combined tumor with histologic features of both malignant melanoma and a squamous cell carcinoma, a squamomelanocytic tumor. An 82-year-old woman presented with a nondescript, skin-colored, firm papule on her nose. Histology showed 2 different neoplastic cell proliferations: atypical squamoid cells and irregularly shaped nests of atypical pigmented epithelioid cells (melanocytes) arranged in small to large nests at the dermal-epidermal junction and within the epidermis. Both components were closely admixed and restricted to the epidermis. Immunohistochemistry showed diffuse cytoplasmic reactivity for pancytokeratin in all areas supporting the histopathologic features of a squamous cell carcinoma. S-100 and melanoma antigen recognized by T cells 1 did not stain these areas and showed strong selective positivity for the atypical melanocytic component. A true malignant proliferation of 2 distinct cell phenotypes due to close paracrine interactions is our favored interpretation because of the intimate admixture, distinct immunohistochemical pattern, and unique histologic features. Perhaps, chronic sun damage (facial location and advanced age) and reduced immunity (history of other malignancies, particularly recent history of a basal cell carcinoma) played a complementary role for the development of the squamomelanocytic tumor.

Resolution of severe atopic dermatitis after tacrolimus withdrawal.

Tacrolimus is an immunosuppressive agent used in solid organ and islet transplantation. Its topical form has shown benefit in the treatment of inflammatory skin conditions. Although tacrolimus has a wide spectrum of side effects, dermatological complications related to systemic tacrolimus therapy are limited in the literature. Atopic dermatitis (AD) is a chronic pruritic cutaneous condition that usually begins in infancy and is characterized by an increased Th2 response. We report the case of a patient with type 1 diabetes mellitus (T1DM) and history of AD latent for 10 years who developed severe dermatitis and alopecia 5 months after undergoing allogeneic islet transplantation and initiating a steroid-free immunosuppressive regimen with sirolimus and tacrolimus maintenance. After exclusion of other possible causes for the progression and exacerbation of the clinical presentation of AD, discontinuation of tacrolimus and introduction of mycophe-nolate mofetil resulted in full remission of the symptoms. The beneficial effects of tacrolimus withdrawal suggest a cause–effect relationship between this adverse event and the utilization of the drug. Islet graft function remained stable after modification of the therapeutic regimen (stable glycemic control and unchanged C-peptide).

Trichoscopy and histopathology of follicular keratotic plugs in scalp discoid lupus erythematosus.

Dermoscopy has become an integral part of diagnosing scalp disorders including discoid lupus erythematosus (DLE). Follicular keratotic plugs are a marker of DLE and correlate with the hyperkeratosis and plugging of the follicular ostia with keratotic material. They may be present in acute or chronic lesions and their presence alone or in conjunction with other described dermoscopic features can lead to timely diagnosis and initiation of treatment. We present three cases of scalp DLE and discuss the clinical, dermoscopic and histopathologic features.