Antonio Guilabert

Antineutrophil cytoplasmic antibodies

Much like other autoantibodies (eg, anti-double stranded DNA in systemic lupus erythematosus or antiglomerular basement membrane antibodies in Goodpastures syndrome), antineutrophil cytoplasmic antibodies (ANCA) have provided doctors with a useful serological test to assist in diagnosis of small-vessel vasculitides, including Wegeners granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and their localised forms (eg, pauci-immune necrotising and crescentic glomerulonephritis). 85-95% of patients with Wegeners granulomatosis, microscopic polyangiitis, and pauci-immune necrotising and crescentic glomerulonephritis have serum ANCA. ANCA directed to either proteinase 3 or myeloperoxidase are clinically relevant, yet the relevance of other ANCA remains unknown. Besides their diagnostic potential, ANCA might be valuable in disease monitoring. In addition, data seem to confirm the long-disputed pathogenic role of these antibodies. Present treatments for ANCA-associated vasculitis are not free from side-effects and as many as 50% of patients relapse within 5 years. Accurate understanding of the key pathogenic points of ANCA-associated vasculitis can undoubtedly provide a more rational therapeutic approach.

Enigmatic Kikuchi-Fujimoto disease: a comprehensive review.

To determine the clinicopathologic significance of Kikuchi-Fujimoto disease (KFD) and review the literature on this condition, we conducted a MEDLINE search of English-language articles published between 1972 and December 2003. KFD has a worldwide distribution, and Asiatic people have a higher prevalence. Its pathogenesis remains controversial. Patients are young and seek care because of acute tender, cervical lymphadenopathy and low-grade fever. Histologic findings include paracortical areas of coagulative necrosis with abundant karyorrhectic debris. Karyorrhectic foci consist of various types of histiocytes, plasmacytoid monocytes, immunoblasts, and small and large lymphocytes. There is an abundance of T cells with predominance of CD8+ over CD4+ T cells. Differential diagnosis includes lymphoma, lymphadenitis associated with systemic lupus erythematosus, and even adenocarcinoma. KFD is an uncommon, self-limited, and perhaps underdiagnosed process with an excellent prognosis. Accurate clinicopathologic recognition is crucial, particularly because KFD can be mistaken for malignant lymphoma.

Enigmatic Kikuchi-Fujimoto Disease

To determine the clinicopathologic significance of Kikuchi-Fujimoto disease (KFD) and review the literature on this condition, we conducted a MEDLINE search of English-language articles published between 1972 and December 2003. KFD has a worldwide distribution, and Asiatic people have a higher prevalence. Its pathogenesis remains controversial. Patients are young and seek care because of acute tender, cervical lymphadenopathy and low-grade fever. Histologic findings include paracortical areas of coagulative necrosis with abundant karyorrhectic debris. Karyorrhectic foci consist of various types of histiocytes, plasmacytoid monocytes, immunoblasts, and small and large lymphocytes. There is an abundance of T cells with predominance of CD8+ over CD4+ T cells. Differential diagnosis includes lymphoma, lymphadenitis associated with systemic lupus erythematosus, and even adenocarcinoma. KFD is an uncommon, self-limited, and perhaps underdiagnosed process with an excellent prognosis. Accurate clinicopathologic recognition is crucial, particularly because KFD can be mistaken for malignant lymphoma.

Dermoscopy Improves Accuracy of Primary Care Physicians to Triage Lesions Suggestive of Skin Cancer

PURPOSE Primary care physicians (PCPs) constitute an appropriate target for new interventions and educational campaigns designed to increase skin cancer screening and prevention. The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard clinical examination improves the accuracy of PCPs to triage lesions suggestive of skin cancer. PATIENTS AND METHODS PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training course in skin cancer detection and dermoscopic evaluation, and were randomly assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a 16-month period, 73 physicians evaluated 2,522 patients with skin lesions who attended their clinics and scored individual lesions as benign or suggestive of skin cancer. All patients were re-evaluated by expert dermatologists at clinics for pigmented lesions. Referral accuracy of both PCP groups was calculated by their scores, which were compared to those tabulated for dermatologists. RESULTS Referral sensitivity, specificity, and positive and negative predictive values were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and 79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant differences were found in terms of sensitivity and negative predictive value (P = .002 and P = .004, respectively). Histopathologic examination of equivocal lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye observation and only six by PCPs using dermoscopy (P = .002). CONCLUSION The use of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations.

Prevalence study of nevi in children from Barcelona. Dermoscopy, constitutional and environmental factors.

Background: Malignant melanoma is becoming an increasingly important problem in public health as incidence rates have been increasing continuously in Caucasian populations. Childhood and adolscence is an important time of life for the formation and evolution of nevi, and the presence of a higher number of nevi in early life could predict a major risk of developing melanoma. Objectives: (1) To determine the number of nevi and the dermoscopic pattern predominance in children of our population. (2) To relate it to constitutional and environmental factors. Methods: Clinical and dermoscopic examinations were performed in 180 children aged 1–15 years. A questionnaire including topics such as past history of sunburns, tanning ability, tendency to sunburn, history of sunlight exposure, use of sunscreens, tendency to freckle and family history of cancer was completed in a face-to-face interview with the parents. On clinical examination, we evaluated hair color, eye color, number of nevi and the presence of nevi in specific locations. All melanocytic lesions were examined dermoscopically, and all patterns were registered as present or absent. We also registered the predominant dermoscopic pattern of the child, defined as being present in more than 40% of all of the individual’s nevi. Results: The mean number of moles was 17.5. Male gender, past history of sunburns, facial freckling and family history of breast cancer were independent risk factors for having a higher number of nevi. We found that 61.1% of children had nevi on the face and neck, 17.2% on the buttocks, 11.7% on the scalp, 19.4% had acral nevi and 31.7% had congenital nevi. We found the presence of nevi in some of these locations to be a risk factor for having a higher number of nevi. The most frequent dominant dermoscopic pattern found in our population was the globular type. Interestingly, we found that the homogeneous pattern predominates in the youngest children, the reticular pattern predominates in adolescents and the dominant globular pattern is constant among all ages evaluated. Conclusion: This is the first study clinically and dermoscopically characterizing nevi in children from our population, and evaluating constitutional and environmental risk factors.

Livedo reticularis de las piernas: metodología de diagnóstico y tratamiento

The term livedo reticularis refers to a reddish-violet reticular discoloration of the skin that mainly affects the limbs. It is caused by an interruption of blood flow in the dermal arteries, either due to spasm, inflammation, or vascular obstruction, and is associated with diseases of varying etiology and severity. To establish the cause of livedo reticularis, it is essential to determine its course (chronic, acute, or fulminant), the presence of other cutaneous signs such as nodules, retiform purpura or necrosis, and the possible association of general symptoms or laboratory findings that suggest a particular systemic process. The aim of this review is to describe the diagnosis and treatment of the disease.

The Role of Fcγ Receptor Polymorphisms in the Response to Anti–Tumor Necrosis Factor Therapy in Psoriasis: A Pharmacogenetic Study

IMPORTANCE Variability in genes encoding proteins involved in the immunological pathways of biological therapy may account for the differences observed in outcomes of anti–tumor necrosis factor (TNF) treatment of psoriasis. OBJECTIVE To assess the role of 2 Fcγ receptor (FcγR) polymorphisms in the response to anti-TNF therapy in psoriasis. DESIGN Retrospective series of patients with psoriasis who received anti-TNF therapy(infliximab, adalimumab, or etanercept) from January 1, 2007, through December 31, 2010. Patients were followed up for 12 weeks. SETTING Two psoriasis referral centers. PARTICIPANTS Seventy treatment-naive patients with moderate to severe psoriasis who received anti-TNF agents. INTERVENTION Patients underwent FcγRIIA-H131R and FcγRIIIA-V158F polymorphism genotyping. MAIN OUTCOMES AND MEASURES The Psoriasis Area and Severity Index and the body surface area were assessed at baseline and at treatment weeks 6 to 8 and 12. The polymorphism genotypes were correlated with the treatment outcomes. RESULTS Bivariate analysis showed a nonsignificant association between FcγR low-affinity genotypes and greater improvement in the Psoriasis Area and Severity Index and body surface area at the end of treatment. Conversely, patients harboring high-affinity alleles presented a greater reduction in body surface area at the intermediate point, which remained independent in the multivariate analysis. We also detected an additive effect of both polymorphisms in the multivariate analysis. High-affinity alleles may contribute to a quicker response owing to a more efficient removal of relevant cells expressing TNF. CONCLUSIONS AND RELEVANCE Preliminary results of this pilot study on the pharmacogenetics of FcγR and biological therapy in psoriasis suggest a role with clinical implications for FcγRIIA-H131R and FcγRIIIA-V158F polymorphisms in the outcome of anti-TNF treatment of psoriasis. These results might help dermatologists in guiding therapeutic decisions, especially in very severe cases where a quick response is needed.

Mortality of bullous pemphigoid in the first year after diagnosis: a retrospective study in a Spanish medical centre

Background  Prognosis of patients with bullous pemphigoid (BP) is controversial, with a 1‐year mortality rate ranging from 6% to 48%.

Rituximab in Childhood Pemphigus Vulgaris: A Long-Term Follow-Up Case and Review of the Literature

Pemphigus vulgaris is an infrequent but life-threatening autoimmune blistering disease that is rare in the pediatric age. Although the mainstay of therapy for childhood pemphigus vulgaris (CPV) is steroids, adjuvant immunosuppressive drugs are often needed to control the disease. Thus, an important part of CPV morbidity can be related to treatment. We report the youngest CPV patient described in the English literature, an 18-month-old boy, who has been followed up for 16 years. During this period, the patient has received several immunosuppressive therapies with variable response. He has finally achieved a long-lasting and complete remission with rituximab. Successful treatment with rituximab has previously been reported in 6 cases of CPV, in whom rituximab presented a good side effect profile. Our patient has experienced a chronic and severe clinical course with multiple flares eventually developing vegetative lesions. Since he presented refractoriness to multiple therapies, we administered rituximab. The introduction of this drug led to a dramatic clinical response and a long-term clinical remission. Based on the experience of this case and the data reported in the literature, we believe that rituximab may be a safe and efficacious agent for the treatment of severe CPV.

Familial and sporadic porphyria cutanea tarda: clinical and biochemical features and risk factors in 152 patients.

Porphyria cutanea tarda is the most frequent porphyria and occurs in both sporadic and familial forms. We conducted the current study in a series of 152 consecutive patients with porphyria cutanea tarda attending the Porphyria Unit of the Hospital Clinic of Barcelona, Spain, to update the clinical manifestations of the disease and to study the sex differences, the proportion of familial forms, and the role of different risk factors in this population. Patients were classified as familial and sporadic cases according to erythrocyte uroporphyrinogen-decarboxylase activity and uroporphyrinogen-decarboxylase genotyping. In our cohort, skin fragility and blisters on the hands were the most frequent clinical manifestations. Women more frequently had facial hypertrichosis (84.8%; p = 0.004), affected areas other than the hands and face (33.3%; p = 0.008), and pruritus (27.3%; p = 0.041) compared with men. Of our patients, 11.8% did not present the typical clinical onset of the disease, with facial hypertrichosis and hyperpigmentation the more frequent complaints in these cases. Analysis of risk factors showed a high prevalence of hepatitis C virus infection (65.8%) and alcohol abuse (59.9%), both being more frequent in men (p < 0.001). Hepatitis C virus infection was the only risk factor that showed differences between the sporadic and familial forms in the logistic regression model (odds ratio, 0.05; 95% confidence interval, 0.006-0.46) In conclusion, atypical forms of presentation of porphyria cutanea tarda should be considered in order to prevent delayed diagnosis. We note the sustained role of hepatitis C virus infection in the precipitation of sporadic porphyria cutanea tarda. Therefore, in countries with a high prevalence of hepatitis C virus infection, the absence of such infection in a patient with porphyria cutanea tarda may suggest a possible familial case. Abbreviations: ALT = alanine aminotransferase, F-PCT = familial porphyria cutanea tarda, GGT = gamma-glutamyl transpeptidase, HBV = hepatitis B virus, HCl = hydrogen chloride, HCV = hepatitis C virus, HIV = human immunodeficiency virus, PCT = porphyria cutanea tarda, ROC = receiver operating characteristic, S-PCT = sporadic porphyria cutanea tarda, U/mgHb = coproporphyrinogen formed per hour per mg of hemoglobin, URO-D = uroporphyrinogen decarboxylase.