Use of biological treatments in patients with hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic skin disease which causes a great impact in the quality of life. Multiple therapeutic options have been proposed, and recently the potential use of biological drugs in severe cases has been postulated. MATERIAL AND METHODS: A retrospective study from seven tertiary Spanish centers reviewing the charts of patients with HS treated with biological drugs was performed. Retrieved information included epidemiological data, clinical features, pain intensity, Hurley stage, laboratory data and therapeutic outcomes. RESULTS: Nineteen patients were included in the study; 10 men (52.6%) and 9 women. Eight patients (42%) showed a Hurley severity stage II and 11 a stage III (57.8%). Adalimumab was prescribed as the first biological treatment in nine out of 19 cases (47.3%), whereas infliximab was prescribed in seven cases (36.8%), ustekinumab in two cases (10.5%) and etanercept in one (5.2%). A complete response was observed in three patients (two cases with infliximab and one case with ustekinumab), a partial improvement in 10 patients and in six patients no clinical improvement was noted. One patient referred worsening of the skin symptoms. In 6 cases, a second biological treatment was prescribed. In three of such cases, a partial improvement was noted, whereas in three cases no clinical improvement was observed. In two cases a switch to a third biological drug was indicated, with a partial improvement in one case. DISCUSSION AND CONCLUSIONS: Biological drugs could be a potential and effective therapeutic option for patients with severe HS. Complete and persistent clinical responses are rarely obtained (15%) and partial responses are achieved in approximately 50% of patients. No specific markers for a therapeutic response have been identified. No definitive conclusions regarding the most effective biological drug for HS could be drawn. Higher dosage schedules seem to be associated with higher response rates. The lack of response of one particular drug does not preclude a potential efficacy to another biological treatment.

Evaluation of MYC status in oral lichen planus in patients with progression to oral squamous cell carcinoma.

BACKGROUND: Malignant transformation of oral lichen planus (OLP) to oral squamous cell carcinoma (OSCC) is controversial. C-MYC is a proto-oncogene involved in various solid tumours, including OSCC. OBJECTIVES: To determine MYC status using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in OLP lesions from 10 patients with progression to OSCC (group I) and to compare this with OLP lesions from patients without progression to OSCC (group II). METHODS: We constructed two tissue microarrays with 11 OSCC samples (group IA), 17 OLP samples from the same patients (group IB) and 13 OLP specimens from 12 control patients (group II). FISH evaluation of the MYC gains was determined in 100 nonoverlapping nuclei per sample. IHC evaluation was determined by calculating the percentage C-MYC expression in the epithelial cells. RESULTS: OSCC samples showed MYC copy number gains and C-MYC overexpression in 91% and 73% of cases, respectively. MYC gains were detected in 47% of samples from group IB and were absent from all samples from group II. C-MYC was overexpressed in 87% of cases from group IB and in only 44% of control specimens (group II). The differences in MYC status between groups IB and II were statistically significant. CONCLUSIONS: OLP lesions in patients with progression to OSCC show MYC gains and C-MYC overexpression. In patients with severe OLP, determining MYC status may predict a subgroup of subjects with a higher risk of progression to OSCC.

Lymphogranuloma venereum: a hidden emerging problem, Barcelona, 2011.

From the beginning of 2007 until the end of 2011, 146 cases of lymphogranuloma venereum (LGV) were notified to the Barcelona Public Health Agency. Some 49% of them were diagnosed and reported in 2011, mainly in men who have sex with men. Almost half of them, 32 cases, were reported between July and September. This cluster represents the largest since 2004. This article presents the ongoing outbreak of LGV in Barcelona.

Serum prolactin levels in psoriasis and correlation with cutaneous disease activity.

BACKGROUND: Prolactin (PRL), a neuropeptide secreted by the anterior pituitary gland, possesses a variety of physiological actions. It has been implicated as an important immunomodulator and exerts a proliferative effect in cultured human keratinocytes via specific receptors. Some studies have indicated an increase in serum PRL levels in psoriasis and exacerbation of psoriasis when a prolactinoma is present. AIM: To evaluate the correlation between serum PRL levels and Psoriasis Area and Severity Index (PASI). METHODS: Serum PRL levels were measured in 20 patients (10 mean, 10 women, age range 18-88 years) with plaque-type psoriasis before and after a 6-week period of topical treatment with tacalcitol ointment. Results were compared with a group of 20 healthy volunteers. RESULTS: Serum PRL levels were significantly increased in the psoriatic group compared with the control group (P < 0.001) and were significantly reduced after treatment (P = 0.001). There was a correlation between pretreatment serum PRL levels and PASI (r = 0.33; P = 0.02). CONCLUSIONS: These results indicate that serum PRL levels may serve as a biological marker of psoriatic disease activity.

Multiple genetic copy number alterations in oral squamous cell carcinoma: study of MYC, TP53, CCDN1, EGFR and ERBB2 status in primary and metastatic tumours.

BACKGROUND: Oncogenesis in the oral cavity is believed to result from genetic alterations that cause a stepwise transformation of the mucosa to invasive carcinoma. In oral squamous cell carcinoma (OSCC) multiple cytogenetic abnormalities have been reported, but their practical significance remains uncertain. OBJECTIVE: To evaluate the usefulness of the assessment of CCND1, MYC, EGFR, ERBB2 and TP53 in OSCC and lymph node metastases. METHODS: Fifty-one consecutive samples of OSCC, nine lymph node biopsies showing metastatic spread from OSCC, 16 biopsies diagnosed as oral leucoplakia (OLK), 13 samples corresponding to oral lichen planus (OLP) and 14 samples from normal oral mucosa were included in the study. Clinical and histopathological characteristics were reviewed. The genetic and protein status of the CCND1, MYC, EGFR, ERBB2 oncogenes and the TP53 tumour suppressor gene were assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The obtained results were compared with the clinical characteristics and the outcome of the OSCCs. RESULTS: TP53 gene losses and MYC, ERBB2, CCND1 and EGFR copy number gains and amplifications were detected in a higher proportion in OSCC and lymph node samples than in OLK and OLP samples (P < 0·005). Overexpression of p53, Myc, Cyclin D1, c-erbB-2 and epidermal growth factor receptor (EGFR) was more prevalent in malignant samples than benign samples (P < 0·05). Correlation between FISH and IHC results was demonstrated in MYC, EGFR and CCND1 studies. The presence of two or more genetic abnormalities in the studied loci was exclusively detected in primary and metastatic OSCC. CONCLUSIONS: In our series, genetic abnormalities in TP53, MYC, CCND1, ERBB2 and EGFR detected by FISH were absent in inflammatory lesions, infrequent in precursor lesions and common in tumoral lesions. Evaluation of the genetic status of TP53, MYC, CCND1, ERBB2 and EGFR may be an additional diagnostic tool in distinguishing benign from malignant oral lesions in histopathologically challenging cases.

MYC gene numerical aberrations in actinic keratosis and cutaneous squamous cell carcinoma.

BACKGROUND: The genetic alterations that drive the transition from actinic keratoses (AKs) to cutaneous squamous cell carcinomas (SCCs) have not been defined precisely. Amplification and/or overexpression of the MYC proto-oncogene have been demonstrated in several human, malignant tumours including head and neck SCCs. OBJECTIVES: To evaluate the presence of MYC genomic aberrations in both AKs and SCCs. METHODS: Skin biopsy specimens corresponding to AKs, SCCs and control samples were included in two paraffin-embedded tissue microarrays. MYC cytogenetic profile was evaluated by fluorescence in situ hybridization (FISH). The results obtained were compared with MYC immunohistochemical expression. RESULTS: Twenty-three AKs and 30 SCCs were evaluated. MYC numerical aberrations were observed in eight of 23 (35%) AKs and 19 of 30 (63%) SCCs (P = 0.05). MYC numerical aberrations were more frequent in moderately to poorly differentiated SCCs (77%) when compared with well-differentiated SCCs (25%; P = 0.027). A significant association between copy number gains of MYC by FISH analysis and MYC protein expression was demonstrated. CONCLUSIONS: MYC gains and amplifications are frequent cytogenetic abnormalities in SCCs and may play a relevant role in promoting SCC undifferentiation and tumoral progression.

Role of Leishmania spp. infestation in nondiagnostic cutaneous granulomatous lesions: report of a series of patients from a Western Mediterranean area.

BACKGROUND: Leishmaniasis is a parasitic disease prevalent in countries of the Mediterranean area. OBJECTIVES: The potential role of Leishmania as the aetiological factor for cutaneous granulomatous lesions in a series of patients from a Western Mediterranean area was evaluated. The practical usefulness of Leishmania-specific polymerase chain reaction (PCR) amplification and immunohistochemical techniques in skin biopsy specimens was assessed. METHODS: Twenty-five skin biopsies diagnosed as nonspecific granulomatous dermatoses were included in the study. A panel of histopathological features was blindly evaluated by two independent observers. Only those cases showing nondiagnostic clinicopathological features and lacking demonstrable microorganisms after bacteriological, mycological or mycobacteriological cultures and specific stains (Ziehl-Neelsen, Giemsa, Gram, periodic acid-Schiff stains) were finally selected. Quantitative real-time PCR was performed in all selected samples. In available samples, immunohistochemical detection of specific Leishmania spp. antigens was also performed. RESULTS: From the selected 25 biopsies, Leishmania spp. DNA was detected by real-time PCR in 13 cases. In seven of eight PCR-positive cases the presence of a varying density of amastigotes could also be demonstrated immunohistochemically. CONCLUSIONS: Leishmania infection seems to be an important aetiological factor in cutaneous granulomatous lesions showing nondiagnostic features in endemic areas. In such areas, Leishmania-specific PCR amplification and/or immunohistochemical studies may be useful diagnostic tools. These techniques may be specifically indicated in the evaluation of patients showing nonspecific granulomatous inflammatory infiltrates of unknown aetiology lacking the histopathological evidence of parasites.

Progressive supravenous granulomatous nodular eruption in a human immunodeficiency virus-positive intravenous drug user treated with highly active antiretroviral therapy.

We describe a 41-year-old human immunodeficiency virus-infected woman with a previous history of intravenous drug abuse, who developed multiple linear nodules following the superficial veins on both arms. Histopathological examination disclosed a dermal histiocytic inflammatory reaction with sarcoid-like granuloma formation occasionally showing an intracytoplasmic refractile material in the histiocytic cells. Nodular lesions developed progressively after starting on highly active antiretroviral therapy (HAART) which increased her CD4 cell count and suppressed her viral load. The appearance of latent inflammatory or autoimmune disease following HAART is a well-recognized phenomenon. We consider that this peculiar 'progressive supravenous granulomatous nodular eruption' should be included within the spectrum of the so-called immune reconstitution inflammatory syndrome.

Optimization of narrow-band uvb with a 5% oleic acid cream in the treatment of psoriasis.

Oleic acid is a monounsaturated fatty acid with a known action of penetration enhancer which has been used for various purposes, such as a tanning increaser. Narrow-band ultraviolet B (UVB) is a also first-line treatment for psoriasis. The purpose of this study was to evaluate if the use of a 5% oleic acid emulsion previous to the phototherapy sessions was useful in reducing the total dosage necessary for whitening in patients with psoriasis. Forty-four patients were included, 24 received application of the emulsion before phototherapy and 20 received phototherapy with no emulsion. Patients received the UVB sessions just to achieve a reduction of 80% of the basal PASI. The total dose received and number of sessions were compared within the 2 groups. A reduction in these parameters (29.68 J/cm(2) vs. 18.16 J/cm(2); 24 vs. 19 sessions) was seen in the group that received application of the emulsion. However, this was not statistically significant. The fact that we did not achieve the statistical significance may be due to the small sample size. These results must be cautiously interpreted and confirmed with further studies.

Topical tacrolimus for the treatment of psoriasis on the face, genitalia, intertriginous areas and corporal plaques.

Tacrolimus is an immunosuppressive drug that has proved effective in the treatment of psoriasis when administered systemically. Topically, it seems only useful in thin psoriasis plaques located on the face, genitalia, and intertriginous areas. We present an open-label clinical trial to test the efficacy of 0.1% tacrolimus ointment in patients with psoriasis on the face, intertriginous areas, both, and in corporal plaques. Efficacy was assessed with the evaluation of erythema, desquamation, infiltration, reduction of the PASI, and reduction of itching. A total of 15 patients were enrolled in the study. In all the localizations evaluated, each of the signs (erythema, desquamation, and infiltration) showed a statistically significant improvement when compared to the baseline (p < .001). Itching also improved rapidly. PASI was also reduced from a mean of 12 at baseline to 2.2 at the end of the study. Of the 15 patients, only 2 experienced an adverse effect (13%), which was described as a warm sensation in facial lesions which was transient and self-limited. In conclusion, tacrolimus ointment may be an alternative to classical options for the treatment of psoriasis, not only for intertriginous, genital, and facial areas, but also for corporal plaques without occlusion, with good tolerance.

Treatment of nail psoriasis with 8% clobetasol nail lacquer: positive experience in 10 patients.

BACKGROUND: Treatment of nail psoriasis is difficult. Several topical therapies have been employed with poor results because drug penetration is limited in this localization. Recently, a new formulation containing 8% clobetasol-17-propionate in a colourless nail lacquer vehicle has shown good results in the control of nail psoriasis. OBJECTIVE: To determine the efficacy and safety of 8% clobetasol-17-propionate in a lacquer vehicle in nail psoriasis. METHODS: Ten patients with both nail bed and matrix psoriasis were included in the study. They were treated with a colourless nail lacquer containing 8% clobetasol-17-propionate that was applied once daily for 21 days and then twice weekly for 9 months. RESULTS: Within 4 weeks of therapy there was a reduction of all the nail alterations, including nail pain. Therapeutic response was directly related to the length of therapy. The nail parameters that responded best to therapy were onycholysis, pitting and salmon patches. Subungual hyperkeratosis and splinter haemorrhages on the other hand had moderate and poor improvement, respectively. The treatment was well tolerated in all of the patients and there were no local (i.e. atrophy and sobreinfection) or systemic secondary effects. CONCLUSIONS: The formulation containing 8% clobetasol-17-propionate is a safe, effective and cosmetically highly acceptable treatment for nail bed and matrix psoriasis.