Dario Didona

Etanercept therapy for toxic epidermal necrolysis

BACKGROUND Toxic epidermal necrolysis (TEN) is a severe and potentially lethal drug reaction for which no standard treatment is available. OBJECTIVE To describe a case series of patients with TEN treated with a single dose of etanercept. METHODS We observed 10 consecutive patients with TEN. For each patient, we recorded the presence of comorbidities and all the drugs recently started (ie, in the last month). In all cases, 50 mg of etanercept was administered in a single subcutaneous injection. The clinical severity of disease was computed using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Using the probabilities of death linked to each level of SCORTEN score, we calculated the expected probability of death in our patients. Healing was defined as complete reepithelialization, and a time to healing curve was then obtained using the Kaplan-Meier method. RESULTS All patients promptly responded to treatment, reaching complete reepithelialization without complications or side effects. The median time to healing was 8.5 days. LIMITATIONS This is a small, uncontrolled case series. CONCLUSION These preliminary results suggest the possibility that tumor necrosis factor-alfa may be an effective target for control of TEN, a dangerous skin condition for which no effective cure has yet been found.

Vitiligo: Pathogenesis, clinical variants and treatment approaches ☆

Vitiligo is a common chronic acquired disease of pigmentation whose etiology is unknown, which usually occurs with asymptomatic whitish patch or macule. Although several hypotheses have been proposed in the literature, the leading theory is still the auto-immune etiology linked to specific genetic mutations. Vitiligo can also be associated with several autoimmune diseases, including autoimmune thyroid diseases, alopecia areata, and halo nevi. Sensorineural hearing loss was reported in several vitiligo patients due to a reduction in the number of melanocytes contained in the membranous labyrinth of the inner ear. Because of its complexity, several therapeutic options are available to treat this systemic disease.

Successful use of etanercept in a case of toxic epidermal necrolysis induced by rituximab.

and triglycerides in asteatotic eczema. Pemetrexed predominantly inhibits thymidylate synthetase and other folate enzymes, which are involved in the synthesis of purines and pyrimidines. To the best of our knowledge, these enzymes were not implicated in the epidermal lipids nor in sebum production. Xerosis and eczema craquel e were not associated with folate deficiency and other antifolate drugs (e.g. methotrexate, trimethoprim). Therefore, we postulate that this rare skin toxicity is not directly related to the antifolate mechanism. In conclusion, our case demonstrated that generalized eczema craquel e can be induced by pemetrexed. Further investigation (e.g. patch test) is needed to elucidate the underlying pathomechanism.

Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases

Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such as anti‐tumor necrosis factor agents. Recently, a role of the interleukin‐23/T‐helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult‐onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult‐onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15‐month follow‐up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first‐line treatment for PRP patients refractory to conventional therapies.

Successful treatment of pyoderma gangrenosum with anakinra in a patient with Wiskott-Aldrich syndrome

Dear Editor, Pyoderma gangrenosum (PG) is a rare, chronic, inflammatory disease, characterized by painful papules or pustules that rapidly evolve into ulcers with irregular, undermined, and overhanging violaceous borders (Gameiro, Pereira, Cardoso, & Gonçalo, 2015). PG is more frequent on lower extremities and in women between 20 and 50 years of age (Gameiro et al., 2015). Up to 70% of PG patients show an underlying systemic disease, including inflammatory bowel diseases, arthritis, and hematological malignancies (Gameiro et al., 2015). Wiskott–Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by severe immunodeficiency, thrombocytopenia, and eczema (Buchbinder, Nugent, & Fillipovich, 2014). The WAS gene (Xp11.22–p11.23) encodes the WAS protein, involved in actin polymerization and associated coupling of receptor engagement, signaling events, and cytoskeletal rearrangement (Buchbinder et al., 2014). A 14-year-old Caucasian male presented to our Institute with a 5month history of PG lesions (Figure 1a,b). His personal medical history was positive for WAS. Whole genome sequencing detected the mutation inv(X)g.5721–11840, a rare inversion in WAS gene. In addition, the patient medical history was also positive for arthritis, Henoch– Sch€ onlein purpura, and a Crohn-like colitis, that led to subtotal colectomy and ileostomy. Several therapies were started to manage PG, including systemic metil-prednisolone (5 mg/kg/day), minocycline (100 mg twice daily), cyclosporine (5 mg kg/day), and adalimumab (80 mg at week 0, 40 mg at week 1, followed by 40 mg every 15 days). However, no PG improvement was observed. Therefore, we decided to start anakinra 100 mg once a day. Two months after a complete

Non Melanoma Skin Cancer Pathogenesis Overview

(1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

MAL Daylight Photodynamic Therapy for Actinic Keratosis: Clinical and Imaging Evaluation by 3D Camera.

Non-melanoma skin cancer is the most common skin cancer with an incidence that varies widely worldwide. Among them, actinic keratosis (AK), considered by some authors as in situ squamous cell carcinoma (SCC), are the most common and reflect an abnormal multistep skin cell development due to the chronic ultraviolet (UV) light exposure. No ideal treatment exists, but the potential risk of their development in a more invasive form requires prompt treatment. As patients usually present with multiple AK on fields of actinic damage, there is a need for effective, safe, simple and short treatments which allow the treatment of large areas. To achieve this, daylight photodynamic therapy (DL-PDT) is an innovative treatment for multiple mild actinic keratosis, well tolerated by patients. Patients allocated to the PDT unit, affected by multiple mild−moderate and severe actinic keratosis on sun-exposed areas treated with DL-PDT, were clinically evaluated at baseline and every three months with an Antera 3D, Miravex© camera. Clinical and 3D images were performed at each clinical check almost every three months. In this retrospective study, 331 patients (56.7% male, 43.3% female) were treated with DL-PDT. We observed a full clearance in more than two-thirds of patients with one or two treatments. Different responses depend on the number of lesions and on their severity; for patients with 1–3 lesions and with grade I or II AK, a full clearance was reached in 85% of cases with a maximum of two treatments. DL-PDT in general improved skin tone and erased sun damage. Evaluating each Antera 3D images, hemoglobin concentration and pigmentation, a skin color and tone improvement in 310 patients was observed. DL-PDT appears as a promising, effective, simple, tolerable and practical treatment for actinic damage associated with AK, and even treatment of large areas can be with little or no pain. The 3D imaging allowed for quantifying in real time the aesthetic benefits of DL-PDT’s increasing compliance.

Association between autoimmune disease and cutaneous melanoma with regard to melanoma prognosis.

An association between autoimmune disease and malignant melanoma (MM) has often been reported in the literature as a positive prognostic factor for MM. Consequently, we evaluated the influence of different autoimmune diseases on the prognosis of MM.

Paraneoplastic pemphigus: Insight into the autoimmune pathogenesis, clinical features and therapy

Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed “paraneoplastic pemphigus”. We included also papers in French, German, and Spanish. We found 613 papers for “paraneoplastic pemphigus”. Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.

Histology of Non-Melanoma Skin Cancers: An Update

Non-melanoma skin cancer (NMSC) is the most frequently diagnosed cancer in humans. Several different non-melanoma skin cancers have been reported in the literature, with several histologic variants that frequently cause important differential diagnoses with other cutaneous tumors basal cell carcinoma (BCC) is the most common malignant skin tumor, with different histologic variants that are associated with a greater or less aggressive behavior and that usually may be confused with other primitive skin tumors. Actinic keratosis, Bowen’s disease, keratoacanthoma, and invasive squamous cell carcinoma (SCC) correspond to the other line of NMSC, that may have only local tumoral behavior, easy to treat and with local management (as in the case of actinic keratosis (AK), Bowen’s disease, and keratoacanthoma) or a more aggressive behavior with a potential metastatic spread, as in case of invasive SCC. Therefore, histopathology serves as the gold standard during daily clinical practice, in order to improve the therapeutical approaches to patients with NMSC and to understand the distinct histopathological features of NMSC. Here, we reported the main pathological features of different non-melanoma skin cancers.