Validation in Spanish of a screening questionnaire for the detection of psoriatic arthritis in patients with psoriasis.

OBJECTIVE: A patient self-administered questionnaire [PsA Screening and Evaluation (PASE)] has been developed and validated in English, but has not been tried in Spanish speaking populations. This study aimed to adapt and validate PASE in Spanish to screen Spanish speaking psoriasis patients for signs and symptoms of inflammatory arthritis. METHODS: Initial translation from English to Spanish (forward translation) was performed by two independent translators and the resulting versions were synthesized during a consensus meeting. The questionnaire was tried in a pilot study and resulted in a change in the agreement scale for a frequency scale with wording adaptation [Spanish PASE (PASE-S)]. RESULTS: One hundred and eleven patients were screened with PASE-S; 25 with PsA (without previous treatments), 23 with psoriasis, 22 with psoriasis and OA and 41 with OA without psoriasis. The diagnosis of psoriasis was performed by a dermatologist, and a rheumatologist determined the diagnosis of PsA or OA. Patients with PsA had statistically significant higher symptoms, function and total PASE-S scores compared with those without PsA. Receiver operator curves showed an area under the curve of 0.79 (95% CI 0.69, 0.89) for the total score. A cut-off value ≥34 showed sensitivity of 76%, and specificity of 74.4% for the diagnosis of PsA. CONCLUSION: The validated PASE questionnaire is a self-administered tool that can be used to screen for PsA among patients with psoriasis in a Spanish speaking population. PASE was able to distinguish between symptoms of PsA and OA.

[Coronary artery disease in patients with psoriasis]. / Enfermedad coronaria en pacientes con psoriasis.

In previous reports, psoriasis was associated with an increased rate of coronary artery disease. These data has not been investigated in our population. We performed a cross-sectional study analyzing data from electronic medical records of a health system in Buenos Aires. We included all patients older than 18 years diagnosed with psoriasis between January 1, 2003 and July 31, 2011 and compared them with a control group. Controls were selected randomly by strata of age and sex from the same health system in a 2:1 ratio. We determined the prevalence of cardiovascular risk factors and coronary heart disease. We analyzed the association between psoriasis and coronary artery disease by both univariate and multivariate analyzes. In total, 3 833 subjects were included (1 286 with psoriasis and 2 547 controls). The prevalence of hypertension (50% vs. 38%, p < 0.001), smoking (25% vs. 17%, p < 0.001), diabetes (12% vs. 8%, p < 0.001) and coronary artery disease (4.98% vs. 3.06%, p = 0.003) were higher in the psoriasis group compared to controls. Regardless age and the presence or absence of diabetes, hypertension or smoking, there was a significant association between coronary artery disease and psoriasis (OR 1.48, CI95% 1.04-2.11, p = 0.03). In conclusion, in this population of Buenos Aires, psoriasis patients had a higher prevalence of diabetes, hypertension, smoking, and coronary artery disease. The association between psoriasis and coronary artery disease was independent of the risk factors explored.

Medical resource consumption of moderate/severe psoriasis in a private health organization of Buenos Aires, Argentina.

BACKGROUND: Despite the economic burden of psoriasis for patients and societies, scant information exists regarding the impact and burden of the disease in Argentina. OBJECTIVE: The objective of this study was to estimate medical resource consumption and direct health care costs for patients with moderate/severe psoriasis in Buenos Aires, Argentina from the perspective of the payer. METHODS: Adults with moderate/severe psoriasis (severity was defined as receiving systemic treatment), during January 2010-January 2014, aged 18 years and older, members of the Italian Hospital Medical Care Program with at least 18 months of follow-up were included. All data on hospitalizations, drug prescription, outpatient episodes, consultations, and investigations/tests in the 12 months before inclusion in the study were considered for the estimation of medical resource consumption and direct health care costs. First-quarter 2018 costs were obtained from the IHMCP and converted into US dollars (using the January 2018 exchange rate). RESULTS: A total of 791 patients were included. The mean age at diagnosis was 34±12 years. Almost 65% of the patients had a dermatologist as their usual source of care, 43% had internists, and 14% had rheumatologists. The average yearly direct cost was US$ 5326 (95% CI: 4125-7896) per patient per year. STUDY LIMITATION: The single center design and the retrospective nature are the main limitations. CONCLUSION: This is the first Argentine study that evaluated the costs of moderate/severe psoriasis by taking into consideration the direct medical costs of the disease.

[Analysis of a case series of adult patients with severe atopic dermatitis treated with dupilumab in Argentina]. / Análisis de una serie de casos de pacientes adultos con dermatitis atópica severa tratados con dupilumab en Argentina.

Introduction: Severe atopic dermatitis (AD) treatment is an unmet need, given the limited efficacy and safety of classical systemic treatments (CSTs). Dupilumab is a monoclonal antibody that blocks the signaling of the interleukins that mediate the inflammatory response involved in AD. Methods: the clinical response of a group of patients from Argentina with severe AD and insufficient response and/or toxicity to CSTs who were treated with dupilumab before commercial availability was analyzed. EASI, SCORAD, DLQI scales and analog visual scales of pruritus and sleep were evaluated, during a median follow-up of 189 days. In addition, the incidence of adverse events was analyzed. Results: 20 patients (13 male) were included; median age: 37.5 years; median AD evolution: 20 years; atopic comorbidity: 70%. 100% had received systemic corticosteroids (serious complications: 20%). Main reasons for discontinuation of CSTs were lack of efficacy and occurrence of adverse events. All scores were significantly and steadily reduced, with identifiable clinical response at the second month of treatment. At the end of the follow-up, only 3 patients required concomitant systemic immunosuppressive treatment. Dupilumab was well tolerated, with mild and controllable adverse events. Discussion: Dupilumab is the only biological agent with high efficacy demonstrated in clinical and observational studies. In this case series, its effectiveness was confirmed in difficult-to-treat patients with severe AD and inadequate response to CSTs. The safety profile was favorable and consistent.

Introducción: El tratamiento de la dermatitis atópica (DA) severa es una necesidad insatisfecha, dada la limitada eficacia y seguridad de los tratamientos sistémicos clásicos (TSC). Dupilumab es un anticuerpo monoclonal que bloquea la señalización de las interleuquinas mediadoras de la respuesta inflamatoria involucrada en la DA. Métodos: se analizó la respuesta clínica de un grupo de pacientes de Argentina con DA severa y respuesta insuficiente y/o toxicidad a los TSC que fueron tratados con dupilumab antes de su disponibilidad comercial. Se evaluaron las escalas EASI, SCORAD, DLQI y escalas visuales analógicas de prurito y sueño, durante una mediana de 189 días de seguimiento, así como la incidencia de eventos adversos. Resultados: Se incluyeron 20 pacientes (13 varones); mediana de edad: 37,5 años; mediana de evolución de la DA: 20 años; comorbilidad atópica: 70%. El 100% habían recibido corticoides sistémicos (complicaciones graves: 20%). Los principales motivos de suspensión de los TSC fueron falta de eficacia y aparición de eventos adversos. Los puntajes de todas las escalas se redujeron significativa y sostenidamente, con respuesta clínica evidente al segundo mes de tratamiento. Al final del seguimiento, solo 3 pacientes requerían tratamiento inmunosupresor sistémico concomitante. Dupilumab fue bien tolerado, con eventos adversos leves y controlables. Dsicusión: el dupilumab constituye el único agente biológico con elevada eficacia demostrada en estudios clínicos y observacionales. En esta casuística, se confirmó su efectividad en pacientes con DA severa de difícil tratamiento y respuesta inadecuada a los TSC. El perfil de seguridad resultó favorable y sostenido a mediano plazo.

Bullous pyoderma gangrenosum as a predictor of hematological malignancies.

Pyoderma gangrenosum may precede, coexist or follow diverse systemic diseases. The bullous variety is usually associated with hematologic disorders. From 31 patients with pyoderma gangrenosum diagnosed in our hospital during 10 years, only 2 presented with the bullous type. One patient had previous diagnosis of chronic myeloid leukemia. Both had fast-progressive, painful lesions, and both showed an excellent response to systemic corticosteroids. In less than 3 months the lesions recurred simultaneously with the progression of chronic myeloid leukemia in one patient and with the initial diagnosis of acute myeloid leukemia in the other one. They died in less than four weeks. These findings emphasize the importance of its timely diagnosis. Cutaneous lesions could be the first predictor of an underlying disease.

No detection of c-kit gene mutations in exons 9, 11, 13 and 17 and low CD117 expression in plaque-stage mycosis fungoides.

The growth factor receptor c-kit (CD117) is expressed in immature T-cells and in some advanced forms of mycosis fungoides. c-kit gene mutation results in unrestricted neoplastic proliferation. We aimed to detect by PCR the most frequent exon mutations in seventeen plaque-stage MF patients, in their perilesional skin and in healthy skin donors. We secondarily evaluated CD117 expression by immunohistochemistry in plaque-stage and tumor-stage MF. We detected no mutation in c-kit gene and low CD117 expression was confirmed on atypical cells in one patient. Complete c-kit exon and intron sequences should be assessed and more sensitive sequencing method could be also applied.

Pyoderma gangrenosum: clinical characteristics, associated diseases, and responses to treatment in a retrospective cohort study of 31 patients.

OBJECTIVE: The aim of this study was to describe the clinical characteristics of patients with pyoderma gangrenosum (PG) and to evaluate the association between these characteristics, the treatment followed, and the patient responses, relapses, and mortality rates. MATERIAL AND METHODS: This retrospective cohort study identified adults diagnosed with pyoderma gangrenosum over the duration of 10 years. RESULTS: Thirty-one patients were evaluated; 58% were women and 55% were older than 65 years, 87% presented with the ulcerative type, and 77% showed lower limb compromise. Approximately 74% of the cases were associated with systemic disease. The most frequent were inflammatory bowel disease (32%) and hematologic malignancies (22%). Pyoderma gangrenosum preceded the associated disease in 26% of the patients, all of them were younger than 50 years old (P = 0.059). In 83% of the latter, the diagnosis of associated disease followed the cutaneous lesions within 24 months. Among the 10 patients with inflammatory bowel disease, six required biologic agents to control the pyoderma gangrenosum (P = 0.002). CONCLUSION: Despite the advances that have been made in the treatment of patients with pyoderma gangrenosum, we are still unclear as to the optimal way in which patients should be followed up once the diagnosis is made. The results of our study underline the importance of doing screening tests to detect potential disease, emphasizing patients younger than 50 years old, for a minimum time lapse of 24 months. It is essential to design randomized-controlled trials to understand the most appropriate and effective ways of following up patients with pyoderma gangrenosum.

Mortality in patients with psoriasis. A retrospective cohort study. / Mortalidad en pacientes con psoriasis. Análisis de una cohorte retrospectiva.

BACKGROUND AND OBJECTIVES: The immune and inflammatory pathways involved in psoriasis could favor the development of atherosclerosis, consequently increasing mortality. The objectives of this study were: 1) to assess the mortality of a population with psoriasis compared to a control group, and 2) to assess the prevalence of cardiovascular risk factors. PATIENTS AND METHOD: A retrospective cohort was analyzed from a secondary database (electronic medical record). All patients with a diagnosis of psoriasis at 1-01-2010 were included in the study and compared to a control group of the same health system, selected randomly (1:1). Subjects with a history of cardiovascular disease were excluded from the study. A survival analysis was performed considering death from any cause as an event. Follow-up was extended until 30-06-2015. RESULTS: We included 1,481 subjects with psoriasis and 1,500 controls. Prevalence of cardiovascular risk factors was higher in the group with psoriasis. The average follow-up time was 4.6±1.7 years. Mortality was higher in psoriasis patients compared to controls (15.1 vs. 9.6 events per 1,000 person-year, P<.005). Psoriasis was seen to be significantly associated with increased mortality rates compared to the control group in the univariate analysis (HR 1.58, 95% CI 1.16-2.15, P=.004) and after adjusting for cardiovascular risk factors (HR 1.48, 95% CI 1.08-2.3, P=.014). CONCLUSION: In this population, patients with psoriasis showed a higher prevalence for the onset of cardiovascular risk factors as well as higher mortality rates during follow-up.

Cutaneous phaeohyphomycosis.

BACKGROUND: Phaeohyphomycosis is an infrequent infection in human beings. However, in recent years, its prevalence has augmented in immunosuppressed patients (mostly in solid organ transplanted patients). Infection can be mucocutaneous or disseminated. In the former, the fungus inoculation occurs mainly through traumatism. Lesions may be polymorphic and asymptomatic, isolated or multiple, and are usually localized in exposed areas of the limbs and head. Treatment is not standardized. When possible, surgical resection of the lesion is combined with systemic antifungals. METHODS: We communicate three phaeohyphomycosis cases with cutaneous compromise. RESULTS: The cases we present show diverse clinical characteristics and varied severity and evolution. CONCLUSION: It is important for dermatologists to recognize this cutaneous fungus infection because the diagnosis using microscopic examination and mycological culture depends on the clinical suspicion.

Ultrasound entheseal abnormalities at the distal interphalangeal joints and clinical nail involvement in patients with psoriasis and psoriatic arthritis, supporting the nail-enthesitis theory.

OBJECTIVE: It has been shown that nail involvement in psoriasis is associated with systemic enthesopathy. Our objective was to evaluate the association of nail involvement and enthesopathy at distal interphalangeal joint (DIP) level in psoriasis (PsO) and psoriatic arthritis (PsA) patients. METHODS: Consecutive patients (54 PsO and 56 PsA) seen at the outpatients clinic in this cross-sectional study were included. All patients underwent both clinical and ultrasound (US) assessment on the same day. RESULTS: US revealed enthesopathy in at least 1 DIP joint in 9 patients with PsO (17%, 95% CI: 8-29%) and in 18 patients with PsA (32%, 95% CI: 20-46%). US extensor tendon enthesopathy was detected in a higher proportion of fingers with clinical nail involvement compared with fingers without clinical nail involvement, both in PsO and PsA patients (61.2% vs 16.8%, p < 0.0001 and 60.1% vs 22%, p < 0.0001, respectively). Among patients with PsO, 20% (95% CI: 7-41%) and 14% (95% CI: 4-32%) of those with and without clinical nail involvement showed enthesopathy on US examination, respectively (p = 0.54). Among PsA patients, the prevalence of enthesopathy was 30% (95% CI: 15-49%) for patients with clinical nail involvement and 35% (95% CI: 17-56%) for those without nail involvement (p = 0.71). CONCLUSION: Nail disease was associated with DIP US enthesopathy. There was a significant increased prevalence of extensor tendon enthesopathy in fingers with involved nails both in PsO and PsA, although no association was found between nail involvement and extensor tendon enthesopathy at patients' level. These features might support the nail-entheseal pathogenesis theory at DIP level.

Medical resource consumption of moderate/severe psoriasis in a private health organization of Buenos Aires, Argentina,

Abstract Background: Despite the economic burden of psoriasis for patients and societies, scant information exists regarding the impact and burden of the disease in Argentina. Objective: The objective of this study was to estimate medical resource consumption and direct health care costs for patients with moderate/severe psoriasis in Buenos Aires, Argentina from the perspective of the payer. Methods: Adults with moderate/severe psoriasis (severity was defined as receiving systemic treatment), during January 2010-January 2014, aged 18 years and older, members of the Italian Hospital Medical Care Program with at least 18 months of follow-up were included. All data on hospitalizations, drug prescription, outpatient episodes, consultations, and investigations/tests in the 12 months before inclusion in the study were considered for the estimation of medical resource consumption and direct health care costs. First-quarter 2018 costs were obtained from the IHMCP and converted into US dollars (using the January 2018 exchange rate). Results: A total of 791 patients were included. The mean age at diagnosis was 34 ± 12 years. Almost 65% of the patients had a dermatologist as their usual source of care, 43% had internists, and 14% had rheumatologists. The average yearly direct cost was US$ 5326 (95% CI: 4125-7896) per patient per year. Study limitation: The single center design and the retrospective nature are the main limitations. Conclusion: This is the first Argentine study that evaluated the costs of moderate/severe psoriasis by taking into consideration the direct medical costs of the disease.

Adult purpura fulminans associated with staphylococcal infection and administration of colony-stimulating factors.

Purpura fulminans (PF) is a rare syndrome of progressive haemorragic necrosis due to disseminated intravascular coagulation (DIC) and dermal vascular thrombosis leading to purpura and tissue necrosis. PF is more often associated with either a benign infection or a severe sepsis. Rarely, it has been related to drug intake. We report the case of a 24-year-old female patient who suffered from staphylococcal sepsis and pancytopenia, for which she was treated with antibiotics, granulocyte-colony stimulating factor (G-CSF) and granulocyte/macrophage CSF (GM-CSF). Two days after the last GM-CSF dose, she developed widespread necrotic plaques with erythematous borders and purpura in the breast, arms and legs. Coagulation tests indicated DIC and a skin biopsy showed fibrin thrombi in the superficial dermal vessels. The patient totally recovered after removal of the necrotic tissues and application of skin autografts. Although staphylococcal infection was most probably involved in the development of PF, a role of CSF cannot be excluded in this case.

Lingual ulceration associated with retinoic acid syndrome during treatment of acute promyelocytic leukemia.

BACKGROUND: All-trans retinoic acid (ATRA) is routinely associated with chemotherapy for the treatment of acute promyelocytic leukemia (APL). Several reports of scrotal ulceration induced by this agent have been made in the recent years. AIMS: The aim of this article was to report the first case of a lingual ulceration associated with retinoic acid syndrome (RAS). MATHERIALS AND METHODS: We presented a 32-year-old man with a diagnosis of acute promyelocytic leukemia who received treatment with ATRA. He presented with febrile neutropenia and a lingual ulcer that did not respond to antibiotic and antifungal regimens. He developed weight gain, lower limb edema, polyserositis, and acute renal failure. Retinoic acid syndrome syndrome was diagnosed. RESULTS: An exhaustive attempt to exclude infectious causes was made performing repeated cultures, histologic examinations, and direct immunofluorescence for HSV. No causative agent was identified. Re-epithelialization of the ulcer was achieved with ATRA cessation and treatment with systemic steroids. DISCUSSION: As far as we are concerned, we report the first case of a lingual ulceration associated with RAS. CONCLUSION: It is important for dermatologists to recognize this cutaneous complication of ATRA as it poses many differential diagnoses in neutropenic patients.

No detection of c-kit gene mutations in exons 9, 11, 13 and 17 and low CD117 expression in plaque-stage mycosis fungoides

Abstract: The growth factor receptor c-kit (CD117) is expressed in immature T-cells and in some advanced forms of mycosis fungoides. c-kit gene mutation results in unrestricted neoplastic proliferation. We aimed to detect by PCR the most frequent exon mutations in seventeen plaque-stage MF patients, in their perilesional skin and in healthy skin donors. We secondarily evaluated CD117 expression by immunohistochemistry in plaque-stage and tumor-stage MF. We detected no mutation in c-kit gene and low CD117 expression was confirmed on atypical cells in one patient. Complete c-kit exon and intron sequences should be assessed and more sensitive sequencing method could be also applied.

Bullous pyoderma gangrenosum as a predictor of hematological malignancies

Abstract: Pyoderma gangrenosum may precede, coexist or follow diverse systemic diseases. The bullous variety is usually associated with hematologic disorders. From 31 patients with pyoderma gangrenosum diagnosed in our hospital during 10 years, only 2 presented with the bullous type. One patient had previous diagnosis of chronic myeloid leukemia. Both had fast-progressive, painful lesions, and both showed an excellent response to systemic corticosteroids. In less than 3 months the lesions recurred simultaneously with the progression of chronic myeloid leukemia in one patient and with the initial diagnosis of acute myeloid leukemia in the other one. They died in less than four weeks. These findings emphasize the importance of its timely diagnosis. Cutaneous lesions could be the first predictor of an underlying disease.

Emerging systemic fungal infections.

Systemic mycoses are a heterogeneous group of infections caused by different species of fungi that mainly affect individuals with primary or secondary alterations of immunity. In recent years, there has been an increase in the incidence of infections related to migration, AIDS, and other causes of immunosuppression, such as solid organ and bone marrow transplantation; oncological, hematological, and autoimmune diseases; and the use of new drugs. In this paper, we outline the microbiological and epidemiological characteristics of 3 fungi: Aspergillus spp, Fusarium spp, and Penicillium spp. We describe the clinical manifestations of disease with emphasis on those that should alert the dermatologist to make an early diagnosis. We detail the various tools for early diagnosis, prevention, and the epidemiology of different antifungals available for treatment and their mechanism of action and therapeutic efficacy.

Outcomes in 11 patients with dermatofibrosarcoma protuberans treated with Mohs micrographic surgery.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an uncommon intermediate-grade fibrohistiocytic sarcoma. It occurs most often in adults aged 20-50 years and is associated with local invasion and a high recurrence rate. Uncontrolled local disease or metastases may result in death. Treatment has involved wide excision, Mohs micrographic surgery (MMS) and other approaches. The purpose of the current study was to review our experience with MMS in the treatment of patients with DFSP over the past six years. METHODS: We carried out a retrospective chart review for all patients treated with MMS at the Hospital Italiano de Buenos Aires during a six-year period to October 2009. Patient data included age and sex, site, and prior surgical treatment (if any) of the tumor and details of the Mohs procedure. RESULTS: Eleven patients were treated for DFSP. Four (36.4%) patients had been previously treated with a standard wide excision. Three (27.3%) of the 11 tumors were located on the back, four (36.4%) on the upper extremity, one (9.1%) on the lower extremity, and three (27.3%) on the trunk. Mean lesion size at presentation was 5.16 cm(2), and mean defect size was 12.65 cm(2), yielding a difference of 7.49 cm(2) and a ratio (defect size/lesion size) of 2.45. No tumors recurred after MMS. CONCLUSIONS: The recurrence potential of DFSP is directly related to the extent of resection. Mohs micrographic surgery with continuous histological margin control allows for maximum tissue preservation and low recurrence rates and is rapidly emerging as a first-line treatment modality for this condition.

Reactivation of Chagas' disease: cutaneous manifestations in two immunosuppressed patients.

BACKGROUND: Chagas' disease is a zoonosis caused by a protozoan agent, Trypanosoma cruzi. Patients undergoing immunosuppressive treatment due to organ transplant, malignancies, infections, or chemotherapy may reactivate a preexisting chronic or indeterminate Trypanosoma cruzi infection. METHODS: We present two transplant patients who underwent reactivation of Chagas' disease with cutaneous manifestations after an augmentation in their immunosuppressive therapy. A 38-year-old man was hospitalized on day 69 after receiving an allogeneic bone marrow transplant; he developed multiple painful erythematous plaques with diffuse borders, confined to the right cheek, trunk, thigh, elbows, and feet. A 59-year-old woman with a 14-year history of Chagasic cardiomyopathy presented one month after heart transplantation with a painful infiltrated purpuric plaque on the back of her right leg. RESULTS: In both cases, histologic examination of skin biopsies showed dermal infiltration with intrahistiocytic amastigotes. In one of the reported cases, the Strout method detected parasitemia. Treatments with nifurtimox (600 mg/d) in case 1 and benznidazole (400 mg/d) in case 2 were started. Fever and cutaneous lesions resolved immediately after seven days of treatment. CONCLUSIONS: Reactivation of Chagas' disease is a serious complication that usually occurs in immunocompromised patients. Clinical manifestations include febrile illness occasionally associated with painful skin lesions. Early diagnosis and proper treatment can significantly improve these patients' outcome.