A Case Study Of PAPASH Syndrome And Literature Review

BackgroundPyogenic arthritis,pyoderma gangrenosum,acne and hidradenitis suppurativa(PAPASH)syndrome is a very rare autoinflammatory diseases(AIDs).Partly related to the gene mutation of proline/ serine/ threonine/ phosphatase-interacting protein 1(PSTPIP1)gene.It was first reported by Marzano and other researchers in 2013 and was named after the acronym “PAPASH”.Its clinical features are pyogenic arthritis,pyoderma gangrenosum(PG),acne,and hidradenitis suppurativa(HS),but the order of the disease is uncertain.The joint symptoms were non-infectious,seronegative,recurrent septic arthritis,and the skin lesions were acne,hidradenitis suppurativa and gangrenous pyoderma.The course of the disease was chronic and repeated.The pathogenesis of PAPASH syndrome is unclear.Genetic testing in cases reported by Marzano and other researchers,they showed that it is associated with the missense mutation of exon 10 and 11 of the PSTPIP1 gene,causing the increased activity of interleukin-1(IL-1),and triggering related clinical manifestations.Similar to pyogenic arthritis,pyoderma gangrenosum and acne(PAPA)syndrome.But compared with PAPA symdrome,it increased hidradenitis suppurativa.Thus,they are disease lineage.AIDs is a class of recurrent or persistent inflammatory diseases caused by innate immune defects or disorders proposed in the past two decades.PAPASH syndrome is a such disease and is very rare in clinical practice.Only one case research was reported in China,and 4 cases were reported in foreign literature.ObjectiveTo explore the clinical features,pathogenesis and therapeutic response of PAPASH syndrome,provide a reference for the early diagnosis and treatment of this disease,and improve the life quality of patients.Methods1.Reported 1 case of PAPASH syndrome diagnosed in our hospital;2.In terms of “pyoderma gangrenosum”,“hidradenitis suppurativa”,“acne”,“pyogenic arthritis”,etc.to search the literatures in “Chinese National Knowledge Infrastructure(CNKI)”,“Wanfang database”,“Weipu network(formerly known as: Weipu Journal Resource System Integrated service platform)”;3.In terms of “pyoderma gangrenosum”,“hidradenitis suppurativa”,“acne”,“pyogenic arthritis”,etc.to search the literatures in “PubMed” and “Google Scholar(International Edition)”.4.Inclusion criteria:(1)Aseptic inflammation of joints and skin damage such as PG,HS and acne(including past history);(2)clinical manifestations,auxiliary examination and other information are basically complete;(3)diagnosed as PAPASH syndrome OR pyogenic arthritis,pyoderma gangrenosum,acne and hidradenitis suppurativa syndrome;5.Exclusion criteria:(1)Excluding magazine journal publication catalogues,notices and plans,etc.;(2)Excluding duplicate documents and the same literature on different websites;(3)Excluding advertisements,invalid web pages and other documents not related to PAPASH syndrome;6.Screen relevant literature based on inclusion criteria and exclusion criteria;7.5 cases in total,4 cases were included in the literature,1 case in our hospital.The general condition,clinical characteristics,family history,genetic testing and treatment results were collected,and the results were discussed and summarized.Results1.General informationA total of 5 cases were included,including 1 case in the hospital and 4 cases in the literature.There were 3 males and 2 females,the ratio of male to female is 1.5:1.The age range of the patients was 16 to 44 years old,the median age was 26,and the mean age ± standard deviation was 29.4 ± 10.5.The number of patients aged 20 to 40 was mostly.The age distribution of clinical symptoms: pyogenic arthritis is more than 10 years old;acne mainly occurs in the age of 10 to 20 years old;gangrenous pyoderma and hidradenitis suppurativa are mostly in the 20 to 30 years old.The course of diagnosis was as short as 7 years,the longest was 29 years,the median course was 20 years,and the mean duration of disease ± standard deviation was 19.2 ± 7.47,showing a chronic course.Tips:(1)The disease is rare in clinical practice;(2)The diagnostic criteria are reported later(June 2013);(3)There are misdiagnosis or missed diagnosis in early cases;(4)There is no consensus on the treatment.2.Clinical features2.1 Joint symptoms:The joint symptoms of 5 patients showed local joint swelling and pain,3 cases were past history symptoms,and 2 cases were history of present illness symptoms.Among them,4 cases were involved in multiple joints,and 1 case was repeatedly involved in single joints(knee joints).4 cases involved non-middle-axis joints,and 1 case involved spinal joints.Knee joints,ankle joints,wrist joints,and interphalangeal joints are more affected.2.2 Cutanous lesions:The skin lesions of 5 patients showed acne,gangrenous pyoderma,and hidradenitis suppurativa.The acne in 2 patients was past symptoms.Brown pigmentation and scar formation were seen on the face,chest or back at the time of treatment.The acne in 3 patients was history of present illness symptoms,which was characterized by a large amount of inflammatory papules on the face and/or chest and back.,nodules,cysts,with pigmentation and / or scar formation.The gangrenous pyoderma in 5 patients were all with history of present illness symptoms.The lower extremities were more common.They showed multiple necrotic ulcers with clear borders.The base was dark red granules,uneven,and the surface covered with yellowish white and/or dark brown.Skin,the edge of the lesion is dark red swelling.hidradenitis suppurativa in a patient was past history.At the time of treatment,the skin folds of the armpits and groin were seen as cord-like scars or depressed scars.In 4 patients,hidradenitis suppurativa was history of present illness symptoms and showed skin wrinkles.Pleated parts(axillary,groin),dark red inflammatory papules,nodules,plaques,ulcers in the anal genital area,accompanied by sinuses,abscesses and old scars.One patient had psoriasis vulgaris and there was still erythematous scaly-like psoriasis damage during the visit.3.Laboratory and auxiliary examinationOf the 5 patients in this group,4 patients received hematological examination,3 cases of which had normal blood routine,1 case of white blood cells and platelets increased;1 case of C-reactive protein was abnormal,3 cases were higher than normal;3 cases Rheumatoid factor was negative,1 case was positive;4 cases were negative for antinuclear antibodies.3 cases of the synovial fluid in the affected joint cavity were examined.The neutrophil infiltration was observed under the microscope,and the bacterial culture of the synovial fluid was negative in one case.4 cases of affected joint imaging showed destructive polyarthritis.There was no abnormality in 1 case of electrocardiogram,abdominal color Doppler ultrasound and chest CT examination.4.Histopathological findingHistopathological examination of ulcers at 4 patients showed consistent pathological features of gangrenous pyoderma,which showed epidermal rupture,epidermal intercellular edema,diffuse and dense infiltration of dermal neutrophils.5.Gene testFour patients were tested for PSTPIP1 gene sequence variation,2 cases of which showed PSTPIP1 gene abnormality,which were exon 10 and 11 respectively,c.831G?T nucleotide substitution,resulting in missense mutation and internal p.E277 D mutation.C.36 + 68 G > A,c.137 + 47 G > C,c.562 +114 C > G heterozygous mutation occurred in the intron;PSTPIP1 gene mutation was not detected in exon of 2 patients.6.Treatment responseOf the 5 patients,2 cases received anakinra(IL-1 receptor antagonist)and 2 cases received adalimumab,gangrenous pyoderma,acne,hidradenitis suppurativa,and pyogenic arthritis.Two patients were given oral isoflavone soft capsules orally,and the symptoms of acne were alleviated.Three patients were given oral methylprednisolone,and the symptoms of gangrenous pyoderma were relieved,but recurred after reduction.One case was given orally with thalidomide,and gangrenous pyoderma was healed.One case was given cyclosporine orally,and the lesions of gangrenous pyoderma were healed,but the symptoms of hidradenitis suppurativa was aggravated after the reduction.One patient was given oral dapsone,and the symptoms of hidradenitis suppurativa was controlled.Two patients underwent surgical resection of hidradenitis suppurativa.Five patients were all better.During the follow-up period from 3-6 month,4 patients were stable and no recurrence was found.Conclusions1.PAPASH syndrome is a chronic autoinflammatory disease,characterized by non-infectious,seronegative,recurrent pyogenic arthritis,pyoderma gangrenosum,acne and hidradenitis suppurativa coexist,rarely seen in clinical practice.PSTPIP1 gene mutation is found in some cases.2.Anakinra,adalimumab,methylprednisolone,isotretinoin are effective for this disease.