IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

IL-1ß and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

BACKGROUND: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). OBJECTIVE: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. METHODS: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. RESULTS: Skin samples from CLE/SLE+patients presented higher expression of IL-1ß (ARC-82: p=0.024; SLICC-12: p=0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p=0.0097; SLICC-12: p=0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p=0.0003; SLICC-12: p=0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p=0.0257; SLICC-12: p=0.0285) and CD8+ cells (ARC-82: p=0.0075; SLICC-12: p=0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p=0.0024; SLICC-12: p=0.0116). STUDY LIMITATIONS: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. CONCLUSIONS: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1ß, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Epidermolytic hyperkeratosis: a follow-up of 23 years of use of systemic retinoids.

Epidermolytic hyperkeratosis is a form of ichthyosis normally resistant to topical treatments. Female patient monitored since 1978 diagnosed with epidermolytic hyperkeratosis. Clinical examination showed generalized hyperkeratosis and scaling. Given that no other treatments were available at the time, the patient was initially treated with keratolytic, systemic vitamin A and moisturizers, with no improvement. In 1986, with the development of oral retinoids, etretinate was introduced. In 1998 this was replaced by acitretin. The patient is receiving 25 mg/day after 23 years of using oral retinoids. Significant improvement of the condition and patient's quality of life has been noted.

Hiperceratose epidermolítica: um seguimento de 23 anos de uso de retinoides orais / Epidermolytic hyperkeratosis: a follow-up of 23 years of use of systemic retinoids

A hiperceratose epidermolítica é uma forma de ictiose geralmente resistente a tratamentos tópicos. Relata-se um caso de paciente feminina , em acompanhamento na dermatologia desde 1978, com diagnóstico de hiperceratose epidermolítica. Foi tratada inicialmente com queratolíticos, vitamina A oral, ácido tartárico e emolientes tópicos, porém sem melhora no quadro clínico, já que não haviam disponíveis outros tratamentos na época. Em 1986, com o advento dos retinóides orais, foi introduzido o etretinato, e em 1998, foi substituído pelo acitretin, apresentando excelente resposta terapêutica. No momento a paciente está em uso de acitretin 25 mg/dia, completando 23 anos de uso de retinóides orais, com mínimos efeitos adversos e melhora significativa na qualidade de vida.

Epidermolytic hyperkeratosis is a form of ichthyosis normally resistant to topical treatments. Female patient monitored since 1978 diagnosed with epidermolytic hyperkeratosis. Clinical examination showed generalized hyperkeratosis and scaling. Given that no other treatments were available at the time, the patient was initially treated with keratolytic, systemic vitamin A and moisturizers, with no improvement. In 1986, with the development of oral retinoids, etretinate was introduced. In 1998 this was replaced by acitretin. The patient is receiving 25 mg/day after 23 years of using oral retinoids. Significant improvement of the condition and patient's quality of life has been noted.

Angiokeratoma of the vulva.

Angiokeratomas are benign tumors characterized by ectasia of blood vessels in the papillary dermis associated with acanthosis and hyperkeratosis of the epidermis. Dermatological examination of angiokeratomas of Fordyce is characterized by papular keratotic lesions of erythematous-violet color. They are more common in the scrotum, and vulvar involvement is rarely reported. Histopathology is particularly important to distinguish them from other benign and malignant tumors. The article reports the case of a middle-aged black woman with a history of chronic constipation, varicose veins of the lower limbs and cesarean section performed 20 years ago who had had multiple vulvar angiokeratomas for three months.

Angioceratoma da vulva / Angiokeratoma of the vulva

Os angioceratomas são tumores benignos caracterizados por ectasia dos vasos sanguíneos da derme papilar associada à acantose e hiperceratose da epiderme. Ao exame dermatológico, os angioceratomas de Fordyce caracterizam-se por lesões papulo-ceratóticas de coloração eritemato-violácea. São mais comuns no escroto, sendo raramente relatada a localização vulvar. A histopatologia é particularmente importante para difer enciá-los de outros tumores benignos e malignos. O artigo relata o caso de uma mulher negra de meia idade com história de obstipação intestinal, varizes de membros inferiores e cesárea há 20 anos que apresentava múltiplos angioceratomas vulvares há três meses.

Angiokeratomas are benign tumors characterized by ectasia of blood vessels in the papillary dermis associated with acanthosis and hyperkeratosis of the epidermis. Dermatological examination of angiokeratomas of Fordyce is characterized by papular keratotic lesions of erythematous-violet color. They are more common in the scrotum, and vulvar involvement is rarely reported. Histopathology is particularly important to distinguish them from other benign and malignant tumors. The article reports the case of a middle-aged black woman with a history of chronic constipation, varicose veins of the lower limbs and cesarean section performed 20 years ago who had had multiple vulvar angiokeratomas for three months.

Use of the ML-Flow test as a tool in classifying and treating leprosy.

BACKGROUND: The treatment of leprosy is defined by the classification of patients as paucibacillary (PB) or multibacillary (MB). The WHO (World Health Organization) classifies patients according to the number of lesions, but Ridley-Jopling (R & J) also uses complementary exams, which are difficult to use outside reference services. In 2003, a test called ML-Flow, an alternative to Elisa serology, was developed to help classify patients as PB or MB and decide about their treatment. OBJECTIVES: To assess the agreement between the ML-Flow test and slit skin smears, already largely used for MB detection, and to observe the efficacy of the ML-Flow test in the field. MATERIAL AND METHODS: A retrospective study evaluating the medical records of 55 patients who had not undergone previous treatment, diagnosed as PB or MB according to R & J and subjected to slit skin smears and the ML- Flow test. RESULTS: In MB patients, slit skin smears were positive in 80% of the cases, the ML-flow was positive in 82.5%. Among PB patients, the ML-Flow was positive in 37.5% and slit skin smears were negative in 100% of the cases. The agreement between skin smear and ML-Flow results was 87.5%, with a kappa value of 0.59, p <0.001. CONCLUSION: No laboratory test is 100% sensitive and specific for the correct classification of all forms of leprosy. The ML-Flow test is faster, easier to use, and less invasive than slit skin smears and therefore may be useful when making therapeutic decisions in areas of difficult access to reference services.

Lichen striatus on adult.

Lichen Striatus is an uncommon inflammatory skin eruption of unknown etiology. It rarely affects adults, and it is characterized by abrupt onset of coalescent papules, in a linear disposition, usually on the extremities. Histopathology shows lichenoid reaction involving follicles and glands. Occasionally, there is overlap with linear lichen planus and "blaschkitis", the main differential diagnoses. It is reported here the case of an adult woman with erythematous violaceous papules on the right side of the neck and face, diagnosed with lichen striatus by clinical and histopathological correlation. The atypical findings and the diagnostic difficulty are discussed.

Uso do teste ML-Flow como auxiliar na classificação e tratamento da hanseníase / Use of the ML-Flow test as a tool in classifying and treating leprosy

FUNDAMENTOS: O tratamento da hanseníase é definido pela classificação de pacientes em paucibacilares (PB) e multibacilares (MB). A OMS (Organização Mundial de Saúde) classifica os doentes de acordo com o número de lesões, mas Ridley-Jopling (R&J) utiliza também exames complementares, porém é de difícil utilização fora dos serviços de referência. Em 2003 foi desenvolvido um teste denominado ML-Flow, uma alternativa à sorologia por ELISA para auxiliar na classificação de pacientes em PB e MB e auxiliar na decisão terapêutica. OBJETIVOS: Observar a concordância entre o teste de ML-Flow e baciloscopia de linfa, exame já consagrado para detecção de MB. Analisar a utilidade do teste de ML-Flow em campo. MATERIAL E MÉTODOS: Estudo retrospectivo avaliando prontuário de 55 pacientes virgens de tratamento, diagnosticados como PB ou MB por R&J. Submetidos à baciloscopia e ao teste de ML-Flow. RESULTADOS: Nos MB, a baciloscopia foi positiva em 80 por cento dos casos, o ML-flow foi positivo em 82,5 por cento. Entre os PB, o ML-Flow foi positivo em 37,5 por cento e a baciloscopia do esfregaço foi negativa em 100 por cento dos casos. A concordância entre os resultados da baciloscopia do esfregaço e ML-Flow foi de 87,5 por cento, kappa=0,59, p<0,001. CONCLUSÃO: Nenhum teste laboratorial é 100 por cento sensível e específico para a correta classificação de todas as formas de hanseníase. O ML-Flow é um teste rápido, de fácil manuseio em campo, menos invasivo que a baciloscopia podendo ser útil para auxiliar na decisão terapêutica em locais de difícil acesso a serviços de referência.

BACKGROUND: The treatment of leprosy is defined by the classification of patients as paucibacillary (PB) or multibacillary (MB). The WHO (World Health Organization) classifies patients according to the number of lesions, but Ridley-Jopling (R & J) also uses complementary exams, which are difficult to use outside reference services. In 2003, a test called ML-Flow, an alternative to Elisa serology, was developed to help classify patients as PB or MB and decide about their treatment. OBJECTIVES: To assess the agreement between the ML-Flow test and slit skin smears, already largely used for MB detection, and to observe the efficacy of the ML-Flow test in the field. MATERIAL AND METHODS: A retrospective study evaluating the medical records of 55 patients who had not undergone previous treatment, diagnosed as PB or MB according to R & J and subjected to slit skin smears and the ML- Flow test. RESULTS: In MB patients, slit skin smears were positive in 80 percent of the cases, the ML-flow was positive in 82.5 percent. Among PB patients, the ML-Flow was positive in 37.5 percent and slit skin smears were negative in 100 percent of the cases. The agreement between skin smear and ML-Flow results was 87.5 percent, with a kappa value of 0.59, p <0.001. CONCLUSION: No laboratory test is 100 percent sensitive and specific for the correct classification of all forms of leprosy. The ML-Flow test is faster, easier to use, and less invasive than slit skin smears and therefore may be useful when making therapeutic decisions in areas of difficult access to reference services.

Líquen estriado no adulto / Lichen striatus on adult

Líquen estriado é uma erupção inflamatória incomum, de etiologia desconhecida. Raramente acomete adultos, e é caracterizada pelo surgimento abrupto de pápulas coalescentes, em arranjo linear, usualmente em extremidades. A histopatologia mostra reação liquenóide envolvendo folículos e glândulas. Ocasionalmente há sobreposição com líquen plano linear e "blaschkitis", seus principais diagnósticos diferenciais. Relata-se um caso de mulher adulta com pápulas eritematovioláceas em região cervical e hemiface direitas, cuja correlação clínico-histopatológica permitiu o diagnóstico de líquen estriado. Os achados atípicos e a dificuldade diagnóstica são discutidos.

Lichen Striatus is an uncommon inflammatory skin eruption of unknown etiology. It rarely affects adults, and it is characterized by abrupt onset of coalescent papules, in a linear disposition, usually on the extremities. Histopathology shows lichenoid reaction involving follicles and glands. Occasionally, there is overlap with linear lichen planus and "blaschkitis", the main differential diagnoses. It is reported here the case of an adult woman with erythematous violaceous papules on the right side of the neck and face, diagnosed with lichen striatus by clinical and histopathological correlation. The atypical findings and the diagnostic difficulty are discussed.

Secondary Ekbom syndrome to organic disorder: report of three cases.

The Ekbom syndrome, also known as delusion of parasitosis or acarophobia is an obsessive phobic state in which the patient thinks, imagines or believes that his or her skin is infested by parasites. In the hallucinatory state, he/she removes parts of the skin, identifying them as parasites. It can be primary or secondary to other organic or psychiatric diseases. Generally speaking these patients take a long time to seek for medical support and the dermatologist is almost always the first physician to see them. Here we describe three patients with delusional parasitosis associated with organic disorders.

[Evaluation of the degree of incapacity of patients with a diagnosis of leprosy at a dermatology service in the state of São Paulo]. / Avaliação do grau de incapacidade dos pacientes com diagnóstico de hanseníase em serviço de dermatologia do estado de São Paulo.

UNLABELLED: IINTRODUCTION: Leprosy is a chronic infectious disease that can lead to physical incapacity. METHODS: The medical records of 167 patients diagnosed with leprosy between 2003 and 2007 were reviewed. RESULTS: Most of the patients (60%) presented physical incapacity at the time of diagnosis: 34% with grade I and 26% with grade II. It was observed that the degree of incapacity had a direct correlation with the duration of the disease. CONCLUSIONS: Leprosy is still diagnosed late, which may contribute towards maintaining this endemic disease.

Síndrome de Ekbom secundária a transtorno orgânico: relato de três casos / Secondary Ekbom Syndrome to organic disorder: report of three cases

A Síndrome de Ekbom, também conhecida como delírio de parasitose ou acarofobia, é um estado fóbico obsessivo no qual o paciente pensa, imagina ou acredita que está infestado por parasitas na pele. Em estado alucinatório, retira fragmentos de pele, identificando-os como parasitas. Pode tratar-se de um quadro psiquiátrico primário ou secundário a outros transtornos orgânicos. Geralmente, esses pacientes demoram a procurar ajuda médica, e o dermatologista, quase sempre, é o primeiro profissional procurado. Descrevemos o caso de três pacientes dos quais apresentaram delírio de parasitose, associados a transtornos orgânicos.

The Ekbom syndrome, also known as delusion of parasitosis or acarophobia is an obsessive phobic state in which the patient thinks, imagines or believes that his or her skin is infested by parasites. In the hallucinatory state, he/she removes parts of the skin, identifying them as parasites. It can be primary or secondary to other organic or psychiatric diseases. Generally speaking these patients take a long time to seek for medical support and the dermatologist is almost always the first physician to see them. Here we describe three patients with delusional parasitosis associated with organic disorders.

Avaliação do grau de incapacidade dos pacientes com diagnóstico de hanseníase em serviço de dermatologia do estado de São Paulo / Evaluation of the degree of incapacity of patients with a diagnosis of leprosy at a dermatology service in the state of São Paulo

INTRODUÇÃO: Hanseníase é doença infecciosa crônica que pode levar a incapacidade física. MÉTODOS: Avaliou-se 167 prontuários de pacientes com diagnóstico de hanseníase, no período de 2003 a 2007, para investigação do grau de incapacidade no momento do diagnóstico. RESULTADOS: A maioria (60 por cento) dos pacientes apresentava incapacidade física no momento do diagnóstico; 34 por cento grau I e 26 por cento grau II. Observou-se que há relação direta entre a duração da doença e o grau de incapacidade. CONCLUSÕES: O diagnóstico da hanseníase ainda é tardio e isto pode contribuir para a manutenção da endemia.

IINTRODUCTION: Leprosy is a chronic infectious disease that can lead to physical incapacity. METHODS: The medical records of 167 patients diagnosed with leprosy between 2003 and 2007 were reviewed. RESULTS: Most of the patients (60 percent) presented physical incapacity at the time of diagnosis: 34 percent with grade I and 26 percent with grade II. It was observed that the degree of incapacity had a direct correlation with the duration of the disease. CONCLUSIONS: Leprosy is still diagnosed late, which may contribute towards maintaining this endemic disease.

Recidiva de hanseníase após 24 doses de poliquimioterapia multibacilar / Relapse in leprosy after 24 months o who multidrug therapy

The WHO multidrug therapy has changed the leprosy scenario since its implementation, with a low relapse rate. However, it is still a challenge the duration of treatment for effective cure in patients with high bacillary load. We report in this article a relapse in a patient 9 years after he had finished the therapy. It is also discussed the diagnostic criteria for leprosy relapse and the possibility that some patients require a longer treatment than the usually preconized.

Vasculonecrotic reactions in leprosy.

Multibacillary, lepromatous or borderline leprosy patients may present two types of vasculonecrotic reactions: Lucio phenomenon and that associated with erythema nodosum leprosum. Despite they can be distinguished through clinical and histological characteristics; both are often used as synonyms. It is said that leprosy reaction should be properly classified for therapeutic reasons, since it is well known that in Lucio phenomenon there is not a good response to thalidomide. The authors reported two cases of vasculonecrotic phenomena in lepromatous leprosy sharing clinical and histopathological characteristics of both reaction subtypes. The findings may indicate the spectral nature of the reaction phenomena in leprosy and emphasize the importance of the clinic-pathological correlation for proper classification. Our findings may contribute to the understanding of leprosy reactions pathogenesis, broaden the knowledge about their outcome with standard treatment, and provide the scientific background to design better therapeutic strategies for these complications.

Vasculonecrotic reactions in leprosy

Multibacillary, lepromatous or borderline leprosy patients may present two types of vasculonecrotic reactions: Lucio phenomenon and that associated with erythema nodosum leprosum. Despite they can be distinguished through clinical and histological characteristics; both are often used as synonyms. It is said that leprosy reaction should be properly classified for therapeutic reasons, since it is well known that in Lucio phenomenon there is not a good response to thalidomide. The authors reported two cases of vasculonecrotic phenomena in lepromatous leprosy sharing clinical and histopathological characteristics of both reaction subtypes. The findings may indicate the spectral nature of the reaction phenomena in leprosy and emphasize the importance of the clinic-pathological correlation for proper classification. Our findings may contribute to the understanding of leprosy reactions pathogenesis, broaden the knowledge about their outcome with standard treatment, and provide the scientific background to design better therapeutic strategies for these complications.