Angelo Massimiliano D'Erme

IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions

In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.

Potential Infectious Etiology of Behçet's Disease

Behçets disease is a multisystem inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. The cause of Behçets disease remains unknown, but epidemiologic findings suggest that an autoimmune process is triggered by an environmental agent in a genetically predisposed individual. An infectious agent could operate through molecular mimicry, and subsequently the disease could be perpetuated by an abnormal immune response to an autoantigen in the absence of ongoing infection. Potentia bacterial are Saccharomyces cerevisiae, mycobacteria, Borrelia burgdorferi, Helicobacter pylori, Escherichia coli, Staphylococcus aureus, and Mycoplasma fermentans, but the most commonly investigated microorganism is Streptococcus sanguinis. The relationship between streptococcal infections and Behçets disease is suggested by clinical observations that an unhygienic oral condition is frequently noted in the oral cavity of Behçets disease patients. Several viral agents, including herpes simplex virus-1, hepatitis C virus, parvovirus B19, cytomegalovirus, Epstein-Barr virus and varicella zoster virus, may also have some role.

Vitiligo as a systemic disease

Vitiligo is an acquired depigmentary skin disorder of unknown etiology. Vitiligo is not only a disease of melanocytes of the skin. Human melanocytes are derived from the neural crest and are located on various parts of the body. The involvement of skin melanocytes is the most visible one, but a systemic involvement of melanocytes can be observed. Some types of vitiligo (nonsegmental vitiligo) may also be associated with various diseases, mainly with autoimmune pathogenesis. Vitiligo represents a spectrum of many different disorders with different etiologies and pathogeneses, causing a common phenotype: the loss of melanocytes and/or their products. This phenotype is always consistent with a systemic involvement.

A case of linear porokeratosis treated with photodynamic therapy with confocal microscopy surveillance.

Linear porokeratosis (LP) is a rare clinical porokeratosis variant, which typically presents at birth, but can also develop in adulthood. Differential diagnosis includes linear lichen planus, lichen striatus, linear verrucous epidermal nevus, incontinentia pigmenti and linear Dariers disease. An LP lesion has an increased risk of transformation into a squamous cell carcinoma or basal cell carcinoma. The treatment of LP is contradictory and disappointing in general. We present a case of a 16‐year‐old girl with multiple reddish‐brown macules and depressions on the medial aspect of her right arm, localized from the palmar joint up to shoulder region in a linear pattern. We performed confocal microscopy (CLSM) of multiple lesions and a punch biopsy after receiving informed consent to confirm the diagnosis. After diagnosis confirmation, we performed Photodynamic therapy (PDT). Methyl aminolevulinate cream in a 160 mg/g concentration (Metvix crm) was applied under occlusion on the previously cleaned surface of every single lesion for 3 hours. The lesions were subsequently illuminated with a dose of 37 J/cm2 (Aktilite, PhotoCure ASA, Norway). Two months after the first PDT treatment, the patient came for a third PDT session. Treatment follow‐up was performed 6 months after the initial PDT session. A CLSM image proved an increase in the width of the stratum spinosum to 42–48 μm, mild post‐inflammatory changes were also present. Cosmetic and clinical response up to date at the time of last follow‐up (1 year) was satisfactory. No progression was observed.

Treatment of refractory subacute cutaneous lupus erythematosus with oral isotretinoin: A valid therapeutic option

Subacute cutaneous lupus erythematosus (SCLE) is a common manifestation of cutaneous lupus erythematosus(CLE), and its management often involves a combinations of local and systemic treatment (1,2). We present a case of a 26-year-old Caucasian woman with diagnosis of SCLE that was poorly controlled by several therapies. She was treated during the previous 2 years with prednisone (37,5 to 12,5 mg/day for 3 months), hydroxychloroquine (200 mg/day for 4 months), quinacrine (100 mg/ day for 15 days), azathriopine (50 mg/day for 4 months), and topical treatments without a significant improvement of cutaneous lesions. On physical examination she presented several annular, well-demarcated erythematous plaques on the extensor surface of the forearms, upper back, face, V area of the neck, and on the dorsal surface of the feet. Some lesions presented central clearing; others were covered by thin furfuraceous scaling. (FIG. 1a,b). These lesions appeared about 3 years before consultation. She didn’t present or report fever, arthritis or other systemic symptoms. She has had an abnormal development, including verbal and motor skills. Laboratory analysis revealed normal blood count, positive ANA 1:80, positive anti-Ro-SSA antibodies (52 U/mL), and normal complement level. Lesional lupus band test showed deposit of immunoglobulins, complement, and fibrin at the dermo-epidermal junction. A skin biopsy showed hyperkeratosis, vacuolar alteration along the dermoepidermal interface, and a superficial and deep dermal, perivascular and perifollicular lymphocytic infiltrate, confirming the diagnosis of SCLE. We found in the literature only few reports in 1990s and a recent update of therapeutic option describing the possible use of isotretinoin in CLE (1–4). We decided to treat with oral isotretinoin at the dosage of 40 mg/die (i.e., 0.7 mg/kg), and within 1 month a remarkable improvement was observed. At the end of the treatment, started in March and lasted 5 months, only a post-inflammatory Address correspondence and reprint requests to: Angelo Massimiliano D’Erme, MD, Division of Dermatology, Department of Critical Care Medicine and Surgery, Piazza Indipendenza, 11 50129 Florence, Italy, or email: a.m.derme@gmail.com. The authors declare any affiliation or significant financial involvement in any organizations or entity with a direct financial interest in the subject matter or materials discussed in the manuscript on this page.

Efficacy of ustekinumab in sub-erythrodermic psoriasis: when TNF-blockers fail.

Psoriasis is a chronic inflammatory disease involving the skin, and sometimes joints, ligaments, nails, and mucosal membranes (1). Recently, new biological therapies have been developed in order to manage psoriasis in its specific mechanisms of immune regulation (2). Among biologics, ustekinumab has a peculiar mechanism of action, blocking the activities of interleukin-12 and interleukin-23, and has been shown as being as effective as TNF (tumor necrosis factor)-blockers in the treatment of moderate–severe plaque-type psoriasis resistant to classical systemic therapies (3–5). We present the case of a middle-aged male affected by severe plaque-type psoriasis. During his past disease history, he has been managed with topicals, UVB phototherapies, and then classic systemic treatments (etretinate, metothrexate, and cyclosporine) without reaching satisfactory results. A PASI score of 34 represents the index of disease severity at the time we first evaluated his case. A complete evaluation of the patient showed no contraindications to TNF-blockers. We obtained the patient’s informed consent to administer infliximab at the usual dosing regimen for psoriasis. However, after an initial period of clinical efficacy (PASI score decreased from 34 to 16 at week 14 of treatment), psoriasis did not further improve, so that after 1 year of treatment we decided to interrupt infliximab, in order to correctly switch to another biologic agent and try to increase the clinical response. After 6 weeks from the interruption of infliximab (PASI score = 23.6), the patient was introduced to adalimumab 40 mg forthnightly, which he continued for 3 months without reaching any significant improvement (PASI score lowered from 23.6 to 18.2). Once again, we decided to switch to another anti-TNF alpha blocker, etanercept 100 mg/week (two subcutaneous injections of etanercept 50 mg, per week). Even this last treatment was unsatisfactory, with a PASI score of 22 after 4 months of therapy, thus we decided for a treatment interruption in order to perform a new and complete evaluation of our subject’s overall health status. The patient had to be hospitalized because the onset of sub-erythrodermia (FIG. 1), which occurred about 4 weeks from the last administration of Etanercept. In this emergency, evaluating the severe conditions of the patient, Address correspondence and reprint requests to: Gionata Buggiani, MD, University of Rome “G. Marconi,” Chair of Dermatology and Venereology, Rome, Italy; or e-mail: g.buggiani@gmail.com.

Fissured tongue responding to biologics during the treatment of psoriasis: the importance of detecting oral involvement of psoriasis

Recent studies have provided more evidence that psoriasis can give mucosal lesions, especially oral. Nonspecific lesions such as fissured tongue and geographic tongue are relatively frequent in patients suffering from psoriasis. We report a case of a patient presenting an important improvement of his fissured tongue paralleling the improvement of the cutaneous lesions after a 5‐month systemic therapy with infliximab. The authors think it would be important to consider possible oral lesions in patients suffering from psoriasis in normal practice and to evaluate them introducing specific clinical scales.

Efficacy of treatment with oral alitretinoin in patient suffering from lichen simplex chronicus and severe atopic dermatitis of hands

Lichen simplex chronicus (LSC) is a skin disorder characterized by chronic itching and scratching, which can lead to thick, leathery, brownish skin, sometimes with papules and can be associated with atopic eczema. We report the case of a 52‐year‐old man with a 45‐year atopic condition and presenting LSC in his dorsum. After a 3‐month treatment with alitretinoin at the daily dosage of 30 mg, we have observed a moderate improvement of the hand eczema together with a substantial clinical improvement of LSC and an almost complete resolution of pruritus. We want to report this peculiar case to suggest the use of oral alitretinoin for LSC.

A further experience of propranolol for severe infantile hemangiomas of the face: an observational study

Infantile hemangiomas (IHs) are the most common proliferating embrional tumors of infancy, which are constituted by endothelial cell hyperproliferation. The authors want to report their observations of further 14 patients suffering from complicated IHs involving the facial district who were treated with propranolol. 14 patients, with ages between 3 and 12 months, completed a cycle of treatment with propanolol. The observational study aimed at focusing IHs involving the facial district. The treatment with propranolol showed good to very good results in the major part of the treated young patients. The authors want to report their experience and add more data in the confirmation of the use of β‐blockers for IH (either in efficacy or in safety profile), focusing on the efficacy of propanolol when IHs involve the face.

Skin signs as early manifestations of Hutchinson-Gilford progeria syndrome

Hutchinson–Gilford progeria syndrome (HGPS) is a rare, sporadic, autosomal dominant genetic disorder with phenotypic features of accelerated ageing due to a mutation of the lamin A (LMNA) gene. It arises in infancy and generally leads to death at approximately the age of 13 years.1,–,5 We report the case of a 7-month-old baby with HGPS …