PAPASH综合征一例研究

Pyoderma gangrenosum, acne, pyogenic arthritis, and suppurative hidradenitis syndrome： a case study

患者男，22岁，面颈部、背部、腋窝、腹股沟暗红色丘疹、结节、脓疱、囊肿6年，双下肢多发暗紫红斑块伴溃疡1年，2016年10月31日于郑州大学第一附属医院皮肤科就诊。6年前，患者于某院诊断为痤疮，未予治疗。1年前双下肢出现多发紫红色斑块，后破溃并融合成溃疡，直径1～12 cm。2002年5月9日，患者因左膝关节肿痛半年就诊于郑州大学第一附属医院小儿内科，检查示类风湿因子阴性，左膝关节腔积液涂片：中性粒细胞、少量淋巴及单核细胞，未见异常细胞，诊断为左膝化脓性关节炎。入院体检：一般情况欠佳，行走困难，血压142/92 mmHg（1 mmHg = 0.133 kPa）。双下肢多发紫红色斑块，中央溃疡形成。下肢溃疡边缘皮损组织病理：表皮破溃，细胞间水肿，可见中性粒细胞进入，真皮浅中层明显水肿，局灶红细胞外溢，中性粒细胞、淋巴细胞、组织细胞为主弥漫性浸润，临床及病理符合坏疽性脓皮病。面颈部、腰背部可见广泛炎性丘疹、脓疱、脓肿及囊肿，腋窝、腹股沟少量暗红色结节，呈囊肿痤疮及化脓性汗腺炎表现。PSTPIP1基因测序：外显子区未见突变，内含子区发现c.36 ＋ 68 G 〉 A、c.137 ＋ 47 G 〉 C、c.562 ＋ 114 C 〉 G het复合杂合突变，在100例正常人测序中有45例发现该位点突变，考虑为多态性位点，致病意义不能明确。最终诊断：PAPASH综合征。给予甲泼尼龙、头孢米诺、异维A酸及沙利度胺治疗，2周后皮损明显好转。现患者仍在随访中。

A 22-year-old male patient visited the Department of Dermatology of the First Affiliated Hospital of Zhengzhou University on October 31, 2016 due to dark red papules, nodules, pustules and cysts on the face, neck, back and in the axillary and inguinal regions for 6 years, and multiple dark purple plaques and ulcers on bilateral lower limbs for 1 year. Six years ago, the patient was diagnosed with acne in other hospital, and no treatment was given. One year ago, multiple purple plaques occurred on the bilateral lower limbs, which then ruptured and progressed into ulcers with diameters of 1 - 12 cm. On May 9, 2002, the patient visited the Department of Pediatric Medicine of the First Affiliated Hospital of Zhengzhou University due to the left knee joint swelling and pain for half a year. Laboratory examination showed negative rheumatoid factor, and smear examination of the left knee joint effusions revealed that there were neutrophils and a small amount of lymphocytes and monocytes in the joint effusions, and no abnormal cells were observed. Then, the patient was diagnosed with pyogenic arthritis of the left knee. Physical examination at admission showed poor general condition, walking difficulty, slightly increased blood pressure of 142/92 mmHg （1 mmHg = 0.133 kPa）, multiple purple plaques on the bilateral lower limbs with central ulcer formation. Histopathological examination of ulcer margin on the lower limbs showed ulceration, intercellular edema and infiltrating neutrophils in the epidermis, and edema, focal erythrocyte extravasation, diffuse infiltration of neutrophils, lymphocytes and histiocytes in the superficial and middle dermis. Clinical manifestations and pathological features confirmed a diagnosis of pyoderma gangrenosum. There were extensive inflammatory papules, pustules, abscesses and cysts on the face, neck, waist and back, and a small amount of dark red nodules on the axillary and inguinal regions, which were consistent with cystic acne and hidradenitis suppurativa. As PSTPIP1 gene sequencing showed, no mutations were found in exon fragments, while compound heterozygous mutations c.36 ＋ 68 G 〉 A, c.137 ＋ 47 G 〉 C and c.562 ＋ 114 C 〉 G het were found in intron fragments. Among 100 healthy controls, 45 carried the same mutations. So, these mutation sites were considered to be polymorphic sites, and the pathogenicity of these mutations was still unclear. Finally, the patient was diagnosed with PAPASH syndrome. The patient was treated with methylprednisolone, cefminox, isotretinoin and thalidomide, and the lesions were markedly improved after 2 weeks. Now the patient was still followed up.