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Resumen La hidradenitis supurativa (HS) es una enfermedad dolorosa y crónica, que afecta en especial la unidad folículo-pilosebácea de la piel ubicada en ingle, axilas, región perianal, perineo, genitales y submamaria,regiones anatómicas donde se encuentran glándulas sudoríparas apocrinas. El curso clínico de la HS es heterogéneo pues varía desde formas muy graves con abscesos fluctuantes profundos y drenajes eventuales; concicatricesresiduales graves, hasta otra forma de enfermedad comparativamente leve caracterizada por la aparición de algunos nódulos inflamatorios,pústulas ypápulas,de manera recidivante. Comunicamos el caso de un niño de 12 añosde edad, con diagnóstico de hidradenitis supurativa,quien fue tratado con Adalimumab. Realizamos la revisión del estado de arte de esta patología, describimos sus características clínicas, criterios diagnósticos, diagnósticos diferenciales y los posibles tratamientos. Nuestra presentación, tiene por objeto relatar nuestra experiencia en el seguimiento del caso del paciente, y las vicisitudes diagnósticas al respecto, que variaron desde acné inflamatorio grave hasta finalmente arribar al diagnóstico de certeza de hidradenitis supurativa, basándonos en criterios clínicos y ecográficos.Consideramos de interés haber podido emplear el "agente biológico" inhibidordel factor de necrosis tumoral (FNT) que hemos mencionado, con excelente respuesta.
Abstract Hidradenitis suppurativa (HS) is a painful and chronic disease that particularlyaffects the follicle-pilosebaceous unit of the skin located in the groins, armpits, perianal region, perineum, genitals, and submammary glands, which areanatomical regions whereapocrine sweat glands are found. The clinical course of HS is heterogeneous as it varies from very severe forms with deep fluctuating abscesses and eventual drainage; with severe residual scars, to another form ofacomparatively mild condition characterized by the presence of some recurrent inflammatory nodules, pustules and papules as well. We report the case of a 12-year-old boy, diagnosed with hidradenitis suppurativa, who was treated with Adalimumab. We reviewed the state of the art of this pathology, described its clinical characteristics, diagnostic criteria, differential diagnoses and carried out possible treatments. The purpose of our presentation is to report our experience in monitoring the patient's case, along with the diagnostic vicissitudes in this regard, which ranged from severe inflammatory acne to finally arriving at a certain diagnosis of hidradenitis suppurativa, based on clinical and ultrasound criteria. We consider of interest the possibility of having been able to use the "biological agent" inhibitor of the tumor necrosis factor (TNF) that we have mentioned, with an excellent response.
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With the increasing understanding of inflammatory pathogenesis of acne inversa, as well as with the development and application of biological agents in the treatment of autoimmune inflammatory diseases, some biological agents have shown good efficacy and potential for the treatment of acne inversa in clinical research and practice. This review mainly summarizes the research progress in biotherapy of acne inversa in recent years.
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Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in γ-secretase component genes. We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In Ncstn;K5-Cre mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF-α, IL-23A, IL-1β, and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the Ncstn;K5-Cre mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and involved in the malfunction of the skin barrier in the pathogenesis of AI.
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Hidradenitis suppurativa is a chronic inflammatory condition that affects skin regions bearing apocrine glands. Although hidradenitis suppurativa is difficult to treat and cure, the currently available treatments are directed toward managing the lesions and associated symptoms. This review presents an evidence-based outline of the available treatment options. We searched four electronic databases and extracted data from retrieved studies for qualitative or quantitative analysis. Meta-analysis was conducted using the comprehensive meta-analysis software to generate pooled standardized mean differences or risk ratios. Numerous medical treatments are available for hidradenitis suppurativa such as antibiotics, retinoids, antiandrogens, immunosuppressive and anti-inflammatory agents and radiotherapy for early lesions. Adalimumab, an anti-tumor necrosis factor antibody, was superior to placebo in reducing Sartorius score (standardized mean difference = −0.32, confidence interval [−0.46, −0.18], P < 0.0001) and pain (risk ratio = 1.42, confidence interval [1.07, 1.9], P = 0.02), when given weekly (not every other week). Combination therapies (such as antibiotics and hyperbaric oxygen therapy) have been tested, which have shown promising results that are yet to be confirmed. Based on the quality of evidence, the most recommended treatments for hidradenitis suppurativa include adalimumab and laser therapy. Surgery (either by simple excision or complete local excision followed by skin graft) is the first choice for intractable disease presenting in the late stages. However, the evidence on most of these treatments is deficient and further randomized trials are needed to establish the most efficient therapies for hidradenitis suppurativa management.
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Introducción: el síndrome de oclusión folicular está compuesto por acné inverso, acné conglobata y la fístula pilonidal (triada); cuando se asocia la foliculitis disecante del cuero cabelludo entonces constituye la tétrada de oclusión folicular. El acné inverso es una enfermedad supurativa, crónica e invalidante, cuyas características clínicas son la presencia de comedones con múltiples aberturas que vinculan dos o más folículos, abscesos con comunicaciones epitelizadas, y sinus drenantes en regiones con glándulas apocrinas. La génesis de estas afecciones es básicamente genética con expresión dermatológica. Objetivo: caracterizar física e histopatológicamente a los pacientes que padecen de síndrome de oclusión folicular, así como, los resultados del tratamiento quirúrgico de la fístula pilonidal en este trastorno. Método: estudio del comportamiento de la fístula pilonidal en el síndrome de oclusión folicular en 37 enfermos con síndrome de oclusión folicular en Hospital Lenin. Se utilizó la exéresis local de las fístulas pilonidales y perianales, esta exéresis se extendió por el tejido celular subcutáneo hasta la facia. Luego la zona se reparó con injerto libre de piel. Resultados: la fístula pilonidal se presentó en cuatro pacientes de los estudiados con largos períodos evolutivos, los cuales fueron tratados con autoinjerto libre de piel. La hiperqueratosis, así como, la perifoliculitis fueron los cambios histopatológicos de mayor relevancia. Conclusiones: la fístula pilonidal es de difícil manejo en el curso del síndrome de oclusión folicular y solo encuentra solución en el tratamiento quirúrgico con autoinjerto libre de piel.
Introduction: follicular occlusive syndrome includes inverse acne, acne conglobata and pilonidal fistula (triad); when it is associated to the dissecting folliculitis of the scalp then it constitutes the tetrad of follicular occlusion. Reverse acne is a suppurative, chronic and invalidating disease. Its clinical features are the presence of comedones with multiple openings that link two or more follicles, abscesses with epithelial communications, and draining sinuses in regions with apocrine glands. The genesis of these affections is basically genetic with dermatological expression. Objective: to describe physically and histopathologically the patients with follicular occlusion syndrome, as well as the results of surgical treatment of pilonidal fistula in this disorder. Method: the study is on the prevalence of pilonidal fistula in follicular occlusion syndrome in 37 patients with follicular occlusion syndrome. The local excision of the pilonidal and perianal fistulas was performed, this exeresis extended by the subcutaneous cellular tissue until the facia. The area was then repaired with a skin-free graft. Results: four patients had the pilonidal fistula, with long periods of evolution, who were treated with autograft of skin. Hyperkeratosis, as well as, perifolliculitis were the most relevant histopathological changes. Conclusion: the pilonidal fistula is difficult for follicular occlusion syndrome management and only the surgical treatment is the most suitable .
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Objective To measure expressions of nicastrin and its downstream Notch-HES signaling pathwayassociated proteins in skin lesions of patients with acne inversa harbouring nicastrin gene mutations.Methods An immunohistochemical study was performed to measure the expressions of nicastrin and Notch-HES signaling pathwayassociated proteins in paraffin-embeded skin samples from lesions of 4 patients with acne inversa and confirmed nicastrin mutations and from normal skin of 6 human controls.Spearman correlation analysis was carried out to assess the relationship between the expressions of nicastrin and Notch-HES signaling pathway-associated proteins.Results In normal control skin samples,nicastrin was widely distributed in the full-thickness epidermis and skin appendages such as pilosebaceous units,apocrine glands and eccrine glands.However,the expressions of nicastrin and Notch-HES signaling pathway-associated proteins were markedly decreased in the epidermis and hair follicle infundibulum in lesions of patients harbouring nicastrin gene mutations compared with normal control skin.Furthermore,nicastrin expression was positively correlated with Notchl,Notch3 and HES-1 expressions (r =0.831,0.748 and 0.807,P ＜ 0.01,0.05 and 0.01 respectively),but not significantly correlated with Notch2 or HES-5 expressions (r =0.597,0.591 respectively,both P ＞0.05).Conclusion Nicastrin expression markedly decreases in lesions of patients with acne inversa harbouring nicastrin gene mutations,and is positively correlated with the expressions of several Notch-HES signaling pathway-associated proteins,suggesting that the decrease in nicastrin expression may take part in the pathogenesis of acne inversa by influencing the expression of the downstream Notch-HES signaling pathway.
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Objective To analyze γ?secretase gene mutations in a pedigree with acne inversa. Methods Clinical data were collected from a pedigree with acne inversa, which contained 30 members spanning 4 generations. Of these members, 12 were affected by acne inversa, and 9 of the affected members were alive. Peripheral blood DNA was obtained from the proband, his seven relatives (including 4 affected and 3 unaffected members), and 100 unrelatedhealthy human controls. PCR was performed to amplify all the coding exons and their flanking sequences of the NCSTN, PSEN1, PSENEN, Aph1 genes followed by DNA sequencing. Results A heterozygous insertion mutation (c.229_230insCACC)of the PSENEN gene, which led to translational frameshifting and resulted in dysfunciton of the PSENEN protein, was detected in all the 5 patients, but not in unaffected members or healthy controls. Conclusion There is a novel heterozygous insertion mutation c.229_230insCACC in the PSENEN gene, which may be the molecular basis of acne inversa in this family.
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La hidradenitis supurativa es una entidad crónica, debilitante, que afecta las regiones axilares, perineo y submamarias. Se describe una prevalencia del 4 por ciento y su causa tiene que ver con oclusión folicular más que con un proceso de inflamación o de infección de las glándulas apocrinas. Su inicio es en la pubertad con nódulos inflamatorios recurrentes que se rompen espontáneamente o coalescen formando lesiones dérmicas y abscesos dérmicos profundos y dolorosos que dejan eventualmente cicatrices fibrosas, extensas y deformantes. Los tratamientos médicos clásicos o más recientes como inhibidores de FNT- alfa se pueden realizar en etapas tempranas pero la cirugía y últimamente el láser es lo que da mejor resultado en etapas más avanzadas. En esta primera parte abordamos el tema con su epidemióloga, etiología, clínica, diagnóstico y diagnóstico diferencial. En la parte II se revisará enfermedades asociadas, complicaciones y tratamiento.
Hidradenitis suppurativa is a chronic and often debilitating disease affecting primaraly the axillae, perineum, and inframammary regions. A prevalence of 4 percent has been estimated and its etiology includes follicular occlusion rather than an inflammatory and infectious process of the apocrine glands. It start usually in puberty with recurrent inflammatory nodules, that rupture spontaneously or coalesce forming painful and deep dermal abscesses followed eventually by extensive, fibrous and disfigured scars. Medical treatments are useful ininitial stages of the disease like alpha tumor necrosis factor inhibitors but surgery and recently lasers are the solution for better results in advanced stages. In this first section epidemiology, etiology, clinical picture, diagnosis and differential diagnosis are reviewed. In the second section associated diseases, complications and treatment will be revised.
Sujets)
Humains , Hidrosadénite suppurée/diagnostic , Hidrosadénite suppurée/étiologie , Diagnostic différentiel , Hidrosadénite suppurée/épidémiologie , Facteurs de risqueRésumé
La Hidrosadenitis Supurativa (HS) es una enfermedad inflamatoria,folicular, crónica, recurrente y debilitante de la piel, caracterizadapor la presencia de abscesos y/o nódulos recurrentes, formación de fístulas y cicatrices. Las lesiones inflamatorias son dolorosas profundas y se localizan en zonas del cuerpo que poseen glándulas sudoríparas apocrinas, principalmente en la región axilar, inguinal y anogenital. Es una patología que presenta gran retraso en laconsulta y diagnóstico, ya que la mayoría de los casos leves sonreportados tardíamente. La resolución espontánea es poco probable y la discapacidad progresiva es comúnmente experimentada. Hay gran compromiso de la calidad de vida el que se correlaciona con la gravedad de la enfermedad. En esta segunda parte revisaremos las enfermedades asociadas a HS, complicaciones y alternativas terapéuticas de tipo médico y quirúrgico.
Hidradenitis suppurativa (Hs) is a chronic inflammatory, follicular,recurrent and debilitating disease characterized by painful and recurrent nodules forming extensive, fibrous anddisfigured scars. Inflammatory lesions are painful and affect primarily the axillae, inguinal and anogenital areas. Is a late disease in being diagnosed because of late consultation andreport. Spontaneous resolution is very rare and progressive disable is common. There is great quality of life involvementand related with the severity of the disease. In this second Part associated diseases, complications, and medical and surgery treatments are discussed.
Sujets)
Humains , Hidrosadénite suppurée/complications , Hidrosadénite suppurée/thérapieRésumé
This corresponds to an inflammatory disease of the apocrine glands, distributed mainly in the axillary, perineal and perianal regions, clinically characterized by pain, swelling, and smelly discharge. Treatment is expensive, long and leaves large scars, generating economic and psychological problems for the patient. Magnetic resonance imaging (MRI) helps to confirm the diagnosis and determine its extension, which allows it to be distinguished from other entities and to choose the best treatment. To our knowledge, there is only one review of literature dedicated to the characteristics of this pathology using MRI, therefore we present an illustrated literature review in different patients treated at our center.
Corresponde a una enfermedad inflamatoria de las glándulas apocrinas, distribuidas principalmente a nivel axilar, perineal y perianal, caracterizado clínicamente por dolor, tumefacción y secreción mal oliente. Su tratamiento es costoso, largo y deja grandes cicatrices, generando problemas económicos y psicológicos para el paciente. La resonancia magnética (RM) ayuda a confirmar el diagnóstico y a determinar su extensión, lo que permite diferenciarlo de otras entidades y elegir el mejor tratamiento. A nuestro conocimiento, existe sólo una revisión de la literatura dedicada a las características de esta patología en resonancia magnética, por lo que presentamos una revisión de la literatura ilustrada en diferentes pacientes tratados en nuestro centro de atención.
Sujets)
Humains , Hidrosadénite suppurée/diagnostic , Imagerie par résonance magnétique , Hidrosadénite suppurée/physiopathologie , Hidrosadénite suppurée/thérapieRésumé
Objective To detect γ-secretase gene mutations in a large Chinese pedigree with acne inversa (AI).Methods Clinical evaluation was carried out in a large pedigree with AI through field investigation.Peripheral blood samples were obtained from 17 family members (11 affected and 6 unaffected) and 100 unrelated healthy human controls.DNA was extracted from the blood samples,and PCR was performed to amplify all the coding regions of PSEN 1,PSENEN and NCSTN genes followed by DNA sequencing analysis.Results There were 67 members over 5 generations in this family,of whom,25 (13 males and 12 females) were affected by AI.AI was inherited in an autosomal dominant manner in this family.Skin lesions were mainly distributed on the neck,back,chest and buttocks,and occasionally in subaxillary regions.DNA sequencing revealed a novel missense mutation,c.1258C＞ T (p.Q420XP),in the exon 11 of the NCSTN gene in 11 affected family members,which leads to a substitution of glutamine by a premature termination codon at amino acid 420 (p.Q420X).The mutation was undetected in either the unaffected members or the unrelated healthy controls,and had not been registered in the single nucleotide polymorphism (SNP) database in National Center for Biotechnology Information.Conclusions There is a novel heterozygous missense mutation,c.1258C ＞ T in the exon 11 of the NCSTN gene,which may be the molecular basis of pathogenesis of AI in this family.
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Objective To analyze the clinical characteristics and treatment of acne inversa.Methods Seventeen outpatients with acne inversa were collected in the Institute of Dermatology,Chinese Academy of Medical Sciences and Peking Union Medical College from January l,2012 to December 31,2012.The general condition,clinical feature and treatment of these patients were retrospectively analyzed.Results All the patients were male with the age at onset being about 20 years and disease duration varying from 2 to 50 years.Characteristic clinical manifestations were recurrent tender inflammatory papules,nodules,abscesses,fistulae and sinus tracts in the neck,axillary fossa,groin,perineum and buttocks.Among these patients,10 had a family history and seven were sporadic with mild symptoms.Oral tretinoin combined with antibiotics were the main treatment,and surgical treatment was usually used for severe patients.Conclusions Acne inversa is mainly manifested as abscess,sinus and scars in areas bearing apocrine sweat glands,and therapeutic regimen should be selected according to the severity of lesions.