RESUMEN
Pachydermoperiostosis is a rare hereditary disease, which presents with the cutaneous manifestations of pachydermia and cutis verticis gyrata. Histological findings in pachydermia frequently include dermal edema, mucin deposition, elastic fiber degeneration, dermal fibrosis and adnexal hyperplasia. However, the severity of these findings varies between clinical reports, and a systematic multiple-case clinicopathological correlative analysis has not been performed to date. In the present study, we reviewed the skin biopsy specimens obtained from the pachydermia of six pachydermoperiostosis patients. The severity of the characteristic histological features was semiquantitatively evaluated and correlated with the grade of pachydermia. Dermal edema, mucin deposition and elastic fiber degeneration were observed in all cases. Patients with severe pachydermia had sebaceous gland hyperplasia and fibrosis. These results suggest that the triad of mucin deposition, dermal edema and elastic fiber degeneration are found from very early stage pachydermia, and could be considered diagnostic findings. To ensure an earlier diagnosis of pachydermoperiostosis, a biopsy should be taken when a patient has grade 1 pachydermia to determine the presence of this histological triad.
Asunto(s)
Dermatosis Facial/patología , Osteoartropatía Hipertrófica Primaria/complicaciones , Enfermedades de la Piel/patología , Adulto , Dermatosis Facial/etiología , Frente , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/etiología , Adulto JovenRESUMEN
BACKGROUND: Pachydermoperiostosis (PDP) is a rare genetic disorder characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and finger clubbing. Recently, a homozygous mutation in the gene HPGD, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), was found to be associated with PDP. However, mutations in HPGD have not been identified in Japanese PDP patients. OBJECTIVE: We aimed to identify a novel responsible gene for PDP using whole exome sequencing by next-generation DNA sequencer (NGS). METHODS: Five patients, including 2 patient-parent trios were enrolled in this study. Entire coding regions were sequenced by NGS to identify candidate mutations associated with PDP. The candidate mutations were subsequently sequenced using the Sanger method. To determine clinical characteristics, we analyzed histological samples, as well as serum and urinary prostaglandin E2 (PGE2) levels for each of the 5 PDP patients, and 1 additional patient with idiopathic CVG. RESULTS: From initial analyses of whole exome sequencing data, we identified mutations in the solute carrier organic anion transporter family, member 2A1 (SLCO2A1) gene, encoding prostaglandin transporter, in 3 of the PDP patients. Follow-up Sanger sequencing showed 5 different SLCO2A1 mutations (c.940+1G>A, p.E427_P430del, p.G104*, p.T347I, p.Q556H) in 4 unrelated PDP patients. In addition, the splice-site mutation c.940+1G>A identified in 3 of 4 PDP patients was determined to be a founder mutation in the Japanese population. Furthermore, it is likely that the combination of these SLCO2A1 mutations in PDP patients is also associated with disease severity. CONCLUSION: We found that SLCO2A1 is a novel gene responsible for PDP. Although the SLCO2A1 gene is only the second gene discovered to be associated with PDP, it is likely to be a major cause of PDP in the Japanese population.
Asunto(s)
Dinoprostona/metabolismo , Mutación , Transportadores de Anión Orgánico/genética , Osteoartropatía Hipertrófica Primaria/genética , Adulto , Secuencia de Aminoácidos , Pueblo Asiatico/genética , Análisis Mutacional de ADN , Dinoprostona/sangre , Dinoprostona/orina , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Transportadores de Anión Orgánico/metabolismo , Osteoartropatía Hipertrófica Primaria/etnología , Osteoartropatía Hipertrófica Primaria/metabolismo , Fenotipo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
We describe two patients with SAPHO (synovitis-acne-pustulosis-hyperostosis-ostitis) syndrome who presented some of the classic features of Behcet's disease. The first case is a man diagnosed as SAPHO at 74 years old. His major complaint is pain and swelling of the bilateral sterno-clavicular region for more than 14 years. Another conspicuous complication was bilateral glaucoma and episodes of iritis were recognized during the follow-up period. The second case is a 65-year-old woman, who first consulted us with right knee pain. As she had a past history of palmoplantar pustulosis and anterior chest pain, her sterile knee arthritis was diagnosed as SAPHO. She also had been suffering from recurrent oral aphthous ulceration since 6 months before visiting our hospital. Considering the clinical courses of our two cases and a review of five previously reported cases, these conditions may imply that classic features of Behcet's disease are minor complications of SAPHO syndrome. Human leukocyte antigen typing and frequent association of sacroiliitis in our cases and in the review of the literature for SAPHO syndrome with some of the classic features of Behcet's disease may indicate this condition to be a closely related disease with seronegative spondylo-arthritis.