Effectiveness of guselkumab in patients with facial and/or genital psoriasis: Interim analysis results at Week 12 from the GULLIVER study.

BACKGROUND: Facial (FP) and genital psoriasis (GP) significantly affect patients' quality of life. Despite the advances in treatments, limited data on efficacy and safety are available on these difficult-to-treat areas. Guselkumab is an interleukin (IL)-23 inhibitor which has been proven effective in treating patients with moderate-to-severe plaque psoriasis. OBJECTIVES: The aim of this interim analysis was to report the efficacy and safety of guselkumab in the treatment of patients with FP and/or GP. MATERIALS AND METHODS: GULLIVER is a 52-week Italian observational study to evaluate the effectiveness and safety of guselkumab in a real-life setting in patients with FP and/or GP. Adult patients with facial and/or genital moderate-to-severe psoriasis (sPGA score ≥ 3) were included. The primary endpoint of this analysis was the percentage of patients achieving a facial or genital sPGA score of 0 (clear) or 1 (almost clear), at Week 12. The change in the score of the facial or genital sPGA components in patients with a score ≥3 for each sPGA component was assessed. PASI score in patients with a baseline PASI above or below 10 was evaluated. RESULTS: Overall, 351 patients were included in the study; 83.3% of FP and 76.5% of GP patients achieved the primary endpoint. Similar response rates were observed for the facial or genital sPGA components in patients with a baseline facial or genital sPGA score ≥3 in each component. Among patients with a baseline PASI score >10, mean PASI score improved from 19.0 (SD 8.3) to 2.2 (SD 4.8). Forty-four AEs were observed in 32 patients; two mild and transient AEs (fatigue and nausea) were considered treatment related. No SAEs were observed. CONCLUSIONS: Guselkumab, showing to be effective and safe in treating FP and GP, may be a valid therapeutic option for patients with psoriasis localized in these difficult-to-treat areas.

HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland-bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used. OBJECTIVE: The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome. METHODS: A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex-16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS-PGA). RESULTS: A total of 140 patients (59% women; mean age 34.9 ± 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex-16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS-PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test-retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated. CONCLUSION: Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.

Unexpected parasitosis.

Neotrombicula autumnalis is an arthropod living in the soil and parasitizes animals only in its larval stage. Depending on climatic conditions, one to five life cycles can take place in a single year. Human infestation is probably underestimated and can be easily missed due to non-pathognomonic cutaneous manifestations in absence of systemic signs. We describe a case of human trombiculiasis and discuss the diagnostic and therapeutic management of this 'synanthropic' dermatosis.

Possible role of Helicobacter pylori in diseases of dermatological interest.

Helicobacter pylori is a gram-negative, flagellate, microaerophilic bacterium identified for the first time about 30 years ago, as a pathogenic factor of gastritis and peptic ulcer. Soon after, it was linked to several gastrointestinal and extra-gastrointestinal diseases (hematological, cardiovascular, neurological, pulmonary and ocular diseases, obesity, diabetes mellitus, growth retardation and extragastric MALT lymphoma). Association and possible cause-effect correlation with H. pylori infection were suggested in diseases of dermatological interest such as chronic urticaria, rosacea, Henoch-Schoenleins purpura, idiopathic thrombocytopenic purpura, cutaneous and oral lichen planus, atopic dermatitis, recurrent aphthous stomatitis, systemic sclerosis, psoriasis, Sjögrens syndrome, Behçet's disease, pruritus, alopecia areata, primary cutaneous marginal zone B-cell lymphomas, vitiligo, chronic prurigo, multiformis, prurigo nodularis, leukocytoclastic vasculitis, prurigo pigmentosa, eczema nummulare, primary cutaneous MALT-type lymphoma, sublamina densa-type linear IgA bullous dermatosis, Sweet's syndrome, cutaneous T-cell pseudolymphoma and pemphigus vulgaris. A critical review of the literature up to May 2017 shows clear evidence of H. pylori involvement only for some of the above purported associations, while in the majority of cases data appear contrasting and/or obtained on a not adequately large study population. Further clinical and laboratory research, with more adequate methodological and statistical basis, is required to assess the actual existence and relevance of many purported associations, as well as the possible role of H. pylori and the underlying pathogenic mechanisms.

Cutaneous manifestations in Steinert's disease. Apropos of four clinical cases.

Myotonic dystrophy type 1 (MD1) (OMIM 160900, Steinert disease) is the most common muscular disease, with an estimated worldwide prevalence ranging from 0.5 to 18/10,000 (1). MD1 is an autosomal dominant multisystem disorder that affects skeletal and smooth muscles as well as eyes, heart, endocrine system, and central nervous system. Available data on skin and adnexal involvement that has been demonstrated as a hallmark of the neurological disease are still poor. The aim of this case report-based, mini review on MD1 and skin is to highlight the importance of such superficial signs to be easily detected in the physical examination, and to evaluate the occurrence of these cutaneous manifestations in presence of various degrees of the disease and gene mutations.

Laser treatment of post-thyroidectomy scar.

A good aesthetic result in thyroid surgery is one of the main goals, as this procedure usually involves young women affected in clearly visible anatomical areas. To minimize the detrimental effects of scarring outcome, several therapeutic options have been employed. Lasers may be an alternative choice for prevention and treatment of post-surgical thyroidectomy scar. This paper reviews literature and the current knowledge on this topic. A comprehensive search in the Cochrane Library, MEDLINE and PUBMED databases was performed to identify relevant literature investigating the role of laser therapy in both prevention and treatment of unappealing scarring after thyroid surgery. Laser treatment of post-thyroidectomy scar is emerging with promising clinical outcomes. The greatest efficacy has been seen with vascular-selective and ablative sources. Laser therapy should be taken into account as it represents a valid and safe treatment option.

Duncan's dermatosis: from the "terra firma-forme" to a possible syndromic condition. The story of a dirty disease.

Since its first description by Duncan, Tschen and Knox in 1987 in the former Archives of Dermatology (1), "Terra firma-forme dermatosis" has been variously described in medical literature, representing a strange, probably underestimated, cutaneous disease. During the last 40 years, the condition has been recorded as an undesirable as well as unexplained event, occurring mainly in childhood, characterized by a brownish-black appearance of the whole skin, resembling dirt. Recently, authors described several cases of atypical patterns of the disease, sometimes with impressing topographic clinical pictures, evocative for syndromic phenotypes. Thanks to more careful examination of the tegument, often with the aid of non-invasive diagnostic tools, attention to this disease is growing. This brief review summarizes the state of the art on the topic, through an historical overview of what is known of this 'dirty' dermatosis.

Hard to face: cutaneous malignant melanoma.

An 88-year-old Caucasian man recently sought medical attention due to recrudescence of skin disease in the area of previously excised nodule (in 2002) on the nose dorsum. The original lesion was clinically considered as a pigmented basal cell carcinoma, after which histological examination revealed a superficial spreading melanoma in vertical growth face (Clark level IV; Breslow thickness 2.1 mm) arising from a pre-existing nevus. The adjacent skin also showed significant actinic damage both in the epidermis and in the dermis. A sentinel node was positive (micrometastases of melanoma) and radical lymph node dissection of the neck was performed. Other lymph nodes did not contain metastasis. Computed tomography scans of brain, chest, abdomen and pelvis performed at that time showed no evidence of systemic disease.

Evaluation of cutaneous surface parameters in psoriatic patients.

PURPOSE: The purpose of this study was to compare cutaneous surface parameters in lesional and non-lesional skin of psoriatic patients and in corresponding areas of control subjects. METHODS: Sixty-six psoriatic patients (of any grade of severity, with or without arthritis, without any therapy other than systemic biologic drugs) and 28 healthy controls were enrolled in this observational, case-control study. Exclusion criteria were current or past sebo-psoriasis and seborrheic dermatitis, pustular or erithrodermic psoriasis; treatment with immune-suppressive agents, retinoids, or ultraviolet phototherapy in the last 6 months; topical treatment in the last 2 weeks. Corneometry, sebumetry, and pHmetry were evaluated on non-lesional skin of forehead, cheek, chin and volar region of forearm, and on a psoriatic plaque (on elbow or neighboring areas); in controls, the same areas were considered. RESULTS: Corneometry values were significantly lower in psoriatic plaques vs. elbows of controls. Sebumetry showed significantly higher values in non-lesional forearm skin and plaques of psoriatic patients vs. corresponding areas of controls. pH was significantly lower in all areas in psoriasis. No differences were found between patients treated or not with biologics and with or without arthritis. CONCLUSION: Evaluating surface skin parameters in psoriasis is useful to better understand the etiopathogenic mechanism and could suggest new therapeutic approaches.

Interstitial granulomatous dermatitis demonstrating small, discrete skin-colored papules.

We report the case of a 67-year-old female with a rare variant of interstitial granulomatous dermatitis showing multiple skin-colored papules. Clinically, numerous skin-colored or reddish papules were distributed on her back and posterior thighs with itchy scaly erythema on the upper back. After topical steroid application, skin-colored papules still remained after the disappearance of itchy scaly erythema. Histopathologically, perivascular and interstitial infiltration of lymphocytes and histiocytes with occasional multinucleated giant cells were observed in the superficial and mid reticular dermis, accompanied by mild mucin deposition. Interstitial granulomatous dermatitis is similar to interstitial granuloma annulare, but can be differentiated from it by lesser degrees of collagen degeneration with mucin deposition and frequent association with arthritis or rheumatic diseases. As previously reported, multiple asymptomatic skin-colored papules are considered a rare but distinct variant of interstitial granulomatous dermatitis. Although no apparent underlying disorder has developed in the presented case, careful follow-up needs to be continued.

Pilomatrixoma of the breast in a patient with type 1 myotonic dystrophy: successful surgical approach.

Malherbe’s calcifying epithelioma is an uncommon cutaneous tumour that originates from the matrix cells of hair follicle. It was initially described by Malherbe as a benign calcifying epithelioma. Several ultra-structural and electron-microscopic studies later demonstrated its origin from matrix cells and the term pilomatrixoma was introduced. The treatment of this tumour remains mainly surgical. Malignant cases with post-surgical recurrences have been described in literature and recurrences have been related to an incomplete surgical treatment or tumour aggressiveness. We present the case of 31-year-old female patient with pilomatrixoma of the breast, which was very similar to fibroadenoma, in terms of size and other clinical features. We successfully treated this patient surgically, and the aesthetic results were good, despite the proximity of the tumour to the areola-nipple complex. Fifteen months later, the patient is doing well, free of any clinical local recurrence.

5-hydroxytryptamine and Lyme disease. Opportunity for a novel therapy to reduce the cerebellar tremor?

Lyme boreliosis is caused by the spirochete Borrelia burdorferi, which is transmitted by ticks. A 59 year-old woman developed pyrexia, strong headaches, ataxia, dysarthria and tremor of the limbs after a tick bite. She was unable to work and eat on her own. She was hospitalized three times and diagnosed with cerebellar intention tremor, cerebellar ataxia, dysarthria, bilateral horizontal gaze paralysis and a central lesion of the left facial nerve. There were no pyramidal, sensory or psychiatric disturbances. The brain MRI showed multifocal leucoencephalopathy with many hyperintense areas in both hemispheres, as well as in the left superior pedunculus cerebellaris. Diagnosis was confirmed by serologic examination. Treatment with cephtriaxone, doxycycline, methylprednisolone, cephixime and ciprofloxacine was administered without effect on the tremor, ataxia and horizontal gaze paralysis. Treatment was then administered with 5-hydroxytriptamine (5-HT) in increased doses. The result of the three-month treatment with 5-HT was a gradual diminution of the tremor and the ataxia and an increase in the ability to eat, walk and work independently.

Langerhans cell sarcoma: an unusual microscopic presentation.

A 70-year-old Caucasian male presented to our clinic for a pruritic eruption progressing over several months. He complained of fatigue with a 20-pound weight loss over the past year. On presentation, the patient had browny-yellow to violaceous, purpuric, macular and papular lesions on the legs, arms, lower abdomen and back. Initial biopsy showed an angiocentric infiltrate with a suggestion of intraluminal proliferation; CD31 and Fli-1 positivity suggested either reactive angioendotheliomatosis or an unusual intravascular histiocytosis. Further excisional biopsies demonstrated perivascular collections of cells with ample cytoplasm, prominent nuclear pleomorphism and mitotic activity. The nuclei demonstrated nuclear folding, grooves and indentations. The atypical cells were S100, CD1a and CD56 positive with immunohistochemistry. A diagnosis of Langerhans cell sarcoma (LCS) was made. LCS is a rare, aggressive malignancy that can involve multiple organs including the skin, lymph nodes, lung, bone marrow, spleen, heart, and brain. The skin and lymph nodes are commonly involved, and the cutaneous presentation varies greatly. Immunohistochemistry characteristically shows CD1a and S100 positivity. CD56 expression is uncommon and often portends a poor prognosis. There is no established treatment of LCS due to its rarity. Surgery, radiation, and chemotherapy have been used with varied outcomes. Our patient was treated with prednisone with improvement of cutaneous disease. He did not develop systemic involvement, but died 1.5 years later from complications associated with heart failure. Langerhans cell sarcoma should be considered when faced with an unusual angiocentric infiltrate in which initial immunohistochemical staining results may be misleading.

Uncommon clinical presentation of Kimura’s disease as bilateral retroauricular masses in a young Malian male: successful surgical approach.

We present a case of a 27 year-old Malian male referred to our hospital for two large, painless retroauricolar masses that had appeared two years earlier. Bilateral cervical painless lymphadenopathy was present at physical examination, without any other systemic symptoms. His history was relevant for bilateral Kimura’s disease lesions resected 5 years earlier in the same locations. Lymphocytosis and a mild hypereosinophilia were found in routine blood tests, together with increased total IgE levels. After surgery, histology showed lymphoid infiltrates with reactive prominent germinal centres containing eosinophils, suggesting relapse of Kimura’s disease, in the context of nonencapsulated fibrous proliferation with discontinuous collagen fibers, consistent with keloid. Three months after removal of retroauricular masses, abnormal laboratory findings reverted to normal. To the best our knowledge, this is the first case in literature of bilateral keloid lesions developed after surgery for Kimura Disease and harbouring its histopathologic features. Clinicians should be aware of these unusual reactive phenomena and their possible simulators.

The unwelcome trio: HIV plus cutaneous and visceral leishmaniasis.

Leishmania/Human Immunodeficiency Virus (HIV) coinfection has emerged as an extremely serious and increasingly frequent health problem in the last decades. Considering the insidious and not typical clinical picture in presence of immunosuppressive conditions, the increasing number of people travelling in endemic zones, the ability to survive, within both human and vector bodies, of the parasite, clinicians and dermatologists as the first line should be aware of these kind of "pathologic alliances," to avoid delayed diagnosis and treatment. In this setting, the occurrence of cutaneous lesions can, paradoxically, aid the physician in recognition and approaching the correct staging and management of the two (or three) diseases. Treatment of these unwelcome synergies is a challenge: apart from the recommended anti-retroviral protocols, different anti-leishmanial drugs have been widely used, according with the standard guidelines for visceral leishmaniasis (VL), with no successful treatment regimen still been established.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Carcinoma cuniculatum in course of etanercept: blocking autoimmunity but propagation of carcinogenesis?

Carcinoma cuniculatum (CC) or verrucous squamous cell carcinoma is a rare variant of squamous cell carcinoma with low incidence of metastasis. It mainly affects men during the fifth-sixth decade of life, arising mostly on the weight-bearing surface of the foot, but it can also be found in other body areas. The favorable effects on the psoriatic, rheumatoid, juvenile polyarthritis as well as the ankylosing spondylitis after the application of Tumour Necrosis Factor (TNF)-alpha inhibitors, like etanercept, presume the availability of similarity between the etiopathogenetic mechanisms which are responsible for the generation of the inflammatory cascade. According to the latest studies, the sensitivity of the patients to TNF-alpha inhibitors could be genetically determined and may also be due to certain genetic polymorphisms of the NLP3 and CARD8 zones of the inflammasome. The blocking of the inflammatory reaction within the borderlines of the psoriatic arthritis could also be accepted as something of a double edged sword. There is a growing volume of literary data which informs us of the clinical manifestation, not only of skin, but also of other types of tumors after the application of TNF-alpha inhibitors. This inevitably generates the hypothesis that within a certain group of patients the TNF-alpha inhibitors have some additional, and currently obscure, effects on presumably key regulatory proteins of the so-called extrinsic apoptotic pathway. Other proteins of the human inflammasome could be also implicated in the regulation of the programmed cell death and the carcinogenesis - there are speculations, that the adapter protein, ASC/TMS1, could be one of these. The present study describes the case of a patient who developed a rare form of skin tumor - epithelioma cuniculatum - whilst undergoing etanercept therapy for psoriatic arthritis. Under discussion are the possible critical connections in the complex regulatory networks of the inflammatory processes, the programmed cell death (apoptosis) and the carcinogenesis which, in the near or distant future, could become the objects of a targeted therapy.