Francisco Camacho

Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis : a randomized controlled trial with open-label extension

Background  In previous studies, etanercept 25 mg twice weekly (BIW) or 50 mg BIW significantly reduced disease severity in patients with plaque psoriasis and demonstrated a favourable safety profile.

Frontal fibrosing alopecia: A multicenter review of 355 patients

BACKGROUND To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. OBJECTIVE We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. METHODS This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. RESULTS In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). LIMITATIONS The retrospective design is a limitation. CONCLUSIONS Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment.

Management of facial hyperpigmentation.

Facial and neck pigmentations are the most cosmetically important. They are common in middle-aged women, and are related to endogenous (hormones) and exogenous factors (such as use of cosmetics and perfumes, and exposure to sun radiation). Melasma (chloasma) is the most common cause of facial pigmentation, but there are many other forms such as Riehl’s melanosis, poikiloderma of Civatte, erythrose peribuccale pigmentaire of Brocq, erythromelanosis follicularis of the face and neck, linea fusca, and cosmetic hyperpigmentations.Treatment of melasma and other facial pigmentations has always been challenging and discouraging. It is important to avoid exposure to the sun or to ultraviolet lamps, and to use broad-spectrum sunscreens. Several hypopigmenting agents have been used with differing results. Topical hydroquinone 2 to 4% alone or in combination with tretinoin 0.05 to 0.1 % is an established treatment. Topical azelaic acid 15 to 20% can be as efficacious as hydroquinone, but is less of an irritant. Tretinoin is especially useful in treating hyperpigmentation of photoaged skin. Kojic acid, alone or in combination with glycolic acid or hydroquinone, has shown good results, due to its inhibitory action on tyrosinase. Chemical peels are useful to treat melasma: trichloroacetic acid, Jessner’s solution, Unna’s paste, α-hydroxy acid preparations, kojic acid, and salicylic acid, alone or in various combinations have shown good results. In contrast, laser therapies have not produced completely satisfactory results, because they can induce hyperpigmentation and recurrences can occur. New laser approaches could be successful at clearing facial hyperpigmentation in the future.

Analysis of HLA class I expression in progressing and regressing metastatic melanoma lesions after immunotherapy

Despite the potential efficacy of cancer immunotherapy in preclinical studies, it did not show yet significant positive clinical results in humans with only a small number of cancer patients demonstrating objective tumor regression. This poor clinical outcome can be explained by the generation of sophisticated tumor immune escape mechanism, in particular, abnormalities in the expression of HLA class I antigens. We have studied the expression of HLA class I antigens in ten metastatic lesions obtained from a melanoma patient undergoing immunotherapy. Five lesions were obtained after Interferon-alpha-2b treatment and five after autologous vaccination plus BCG (M-VAX). Eight metastases were regressing after immunotherapy while two were progressing. The eight regressing metastases showed high level of HLA class I expression, whereas the two progressing lesions had low levels as measured by real time PCR and immunohistological techniques. These results indicate a strong association between HLA class I expression and progression or regression of the metastatic lesions. Our data support the hypothesis that the level of HLA class I expression is an important parameter of tumor immune escape that needs to be monitored.

Alopecia Areata, Stress and Psychiatric Disorders: A Review

Although the results of some studies have proven negative, the influence of psychological factors in the development, evolution and therapeutic management of alopecia areata is, in general, well documented. Life events and intrapsychically generated stress can play an important role in triggering of some episodes. The comorbidity of psychiatric disorders, mainly generalized anxiety disorder, depression, and phobic states, is high. The role of treatment of concomitant psychopathological disorders is a vital one. Indeed this treatment can positively affect how the patient adapts to his/her alopecia and social setting and perhaps can even lead to a better dermatological evolution of the alopecia. Therefore, controlled studies analyzing the possible links between psychiatric symptoms, treatment with antidepressants or benzodiacepines, evolution of alopecia, medium term prognosis, and immune function are necessary. Basic psychotherapeutic support may prove to be of use in many cases and can be carried out by the dermatologist, although a subgroup of patients may need psychopharmacological or psychotherapeutic specialized treatments. Studies using operative diagnostic criteria and structured interviews are still scarce. Therefore, it seems necessary to design studies using modern psychiatric methodology. Controlled clinical trials to test the efficiency of psychoactive drugs and psychotherapy in the disease are also needed. By studying in depth these and other related aspects, we may improve the clinical management of our patients.

Economic evaluation of a store-and-forward teledermatology system for skin cancer patients:

We conducted an economic analysis of a store-and-forward teledermatology system for the routine triage of skin cancer patients. A cost-identification, cost-effectiveness and sensitivity analysis under a societal perspective was used to compare teledermatology with the conventional care alternative. In the period March 2004 to July 2005, a total of 2009 teledermatology referrals were managed from 12 Primary Care Centres (PCCs) of the public health system. The unit cost was of €79.78 per patient in teledermatology, and €129.37 per patient in conventional care (P < 0.005), with an incremental cost of €49.59 per patient in favour of teledermatology. The cost ratio between teledermatology and conventional care was 1.6. There was a significant inverse relation between the unit cost in each participating PCC and the number of teleconsultations transmitted from them (P < 0.001). Teledermatology resulted in a more cost-effective, or dominant, methodology. In a public health system equipped with an intranet, the routine use of teledermatology in skin cancer clinics is a cost-effective method of managing referrals.

HLA class I expression in metastatic melanoma correlates with tumor development during autologous vaccination

Our knowledge of the mechanisms underlying tumor-specific immune response and tumor escape has considerably increased. HLA class I antigen defects remain an important tumor escape mechanism since they influence the interactions between tumor cells and specific T and NK cells in the course of malignant disease. We have studied here HLA class I expression in six subcutaneous metastases obtained from a melanoma patient immunized with an autologous melanoma cell vaccine (M-VAX). We report in this paper that HLA class I antigen expression on these metastatic lesions strongly correlated with the course of the disease. The three metastases that were partially regressing at the time of their excision showed a strong HLA class I expression, whereas the progressing ones showed a very weak or negative staining with most of the anti-HLA class I mAbs used. Real-time quantitative PCR of the samples obtained from microdissected tumor tissue revealed a significant difference in the mRNA levels of HLA-ABC heavy chain and β2m between the two types of metastases, i.e., lower levels in progressing metastases and high levels in regressing ones, confirming the immunohistological findings. This is, to our knowledge, the first report where the clinical outcome of different HLA class I positive and negative melanoma metastases can be clearly correlated with the regression and progression of the disease, respectively.

Mutational spectrum of NSDHL in CHILD syndrome

CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects, MIM 308050) is an X linked dominant, male lethal, multisystem birth defect characterised by an inflammatory epidermal nevus showing a unique lateralisation pattern and strict midline demarcation. Hypoplasia or aplasia of skeletal or visceral structures may be found ipsilateral to the major cutaneous involvement.1 Owing to the highly characteristic clinical and histopathological features of the CHILD naevus,2 a diagnosis can be established not only in classical cases (fig 1) but also in cases with minimal or atypical involvement.3 In 2000, mutations in NSDHL (NAD(P)H steroid dehydrogenase-like protein) at Xq28 were identified by some of us to be the cause of this syndrome.4 Four additional NSDHL mutations have subsequently been reported in individuals with CHILD syndrome.5–8 Studies carried out on the murine Nsdhl mutants bare patches (Bpa) and striated (Str) have shown that this gene encodes a 3β-hydroxysteroid dehydrogenase (3β-HSD) that catalyses a step in the post-squalene cholesterol biosynthetic pathway and is localised within membranes of the endoplasmic reticulum and on the surface of intracellular lipid storage droplets.9–11 Non-functional NSDHL might cause the CHILD phenotype through a lack of cholesterol or other sterols downstream of the block in biosynthesis, or by the accumulation of intermediates upstream of the product generated by NSDHL. Figure 1  Thirteen year old patient with CHILD syndrome (case 9, table 1): ichthyosiform nevus showing lateralisation with unilateral distribution and midline demarcation; ipsilateral hypoplasia of arm and hand. Reproduced with permission. A related trait, X linked dominant chondrodysplasia punctata (CDPX2, MIM 302960),22 is caused by mutations in EBP (emopamil binding protein) at Xp11.22–p11.23 that functions similarly in the late cholesterol biosynthesis, downstream of NSDHL .23,24 In the past, a case of X linked dominant chondrodysplasia punctata showing unilateral involvement …

Regression of melanoma metastases after immunotherapy is associated with activation of antigen presentation and interferon-mediated rejection genes

We present the results of a comparative gene expression analysis of 15 metastases (10 regressing and 5 progressing) obtained from 2 melanoma patients with mixed response following different forms of immunotherapy. Whole genome transcriptional analysis clearly indicate that regression of melanoma metastases is due to an acute immune rejection mediated by the upregulation of genes involved in antigen presentation and interferon mediated response (STAT‐1/IRF‐1) in all the regressing metastases from both patients. In contrast, progressing metastases showed low transcription levels of genes involved in these pathways. Histological analysis showed T cells and HLA‐DR positive infiltrating cells in the regressing but not in the progressing metastases. Quantitative expression analysis of HLA‐A,B and C genes on microdisected tumoral regions indicate higher HLA expression in regressing than in progressing metastases. The molecular signature obtained in melanoma rejection appeared to be similar to that observed in other forms of immune‐mediated tissue‐specific rejection such as allograft, pathogen clearance, graft versus host or autoimmune disease, supporting the immunological constant of rejection. We favor the idea that the major factor determining the success or failure of immunotherapy is the nature of HLA Class I alterations in tumor cells and not the type of immunotherapy used. If the molecular alteration is reversible by the immunotherapy, the HLA expression will be upregulated and the lesion will be recognized and rejected. In contrast, if the defect is structural the MHC Class I expression will remain unchanged and the lesion will progress.

Sebaceus naevi: a clinicopathologic study

Objective To analyse sebaceus naevus (SN) incidence, associated malignancies, and developmental defects in a retrospective study.