Clinical and Genetic Findings of the First Report of PAPA Syndrome in Brazil

Background. PAPA syndrome (MIM #604416) is a rare monogenic autoinflammatory disease genetically transmitted in an autosomal dominant trait that results from missense mutations in the proline-serine-threonine phosphatase-interactive protein 1 (PSTPIP1) gene located on chromosome 15 and is characterized by sterile pyogenic arthritis, pyoderma gangrenosum, and cystic acne. We describe the clinical and molecular findings of two related Brazilian patients with PAPA syndrome. Case Presentation. A 7-year-and-3-month-old boy with nonconsanguineous parents had had recurrent pyoarthritis since the age of 5 years and 8 months. During his last and long hospitalization, the lack of improvement with antibiotics, evidence of increased inflammatory activity, repeated arthrotomies, draining purulent fluid that had negative cultures, and the history of trauma, all on in a clinical background of pyoarthritis, led to the suspicion of an autoinflammatory syndrome. This was confirmed by the good clinical response to corticotherapy. Genetic sequencing confirmed the diagnosis of PAPA syndrome, with the pathogenic mutation c.688 G > A (p. Ala230Thr) in the PSTPIP1 gene present in the patient and in the mother. Conclusions. This case illustrates that in children with recurrent/recalcitrant sterile recurrent pyogenic arthritis/osteomyelitis, the possibility of an underlying immunological condition should be considered. In both, recurrent infections or recurrent inflammation, many genes involved in the inborn errors of immunity can be associated, and a correct and precocious diagnosis is necessary to avoid mobility and mortality. To the best of our knowledge, this is the first report of PAPA syndrome in Brazil.

Pioderma gangrenoso

El pioderma gangrenoso (PG) es una dermatosis neutrofílica infrecuente, crónica, dolorosa y recidivante, idiopática en el 25-50% de los pacientes, con una presentación morfológica distintiva pero variable que abarca las formas pustulosas, ampollosa, ulcerativa y granulomatosa superficial o vegetante. De forma característica, en el 20-50% de las ocasiones aparece sobre piel previamente traumatizada; hasta en un 75% de los casos se asocia a una enfermedad sistémica previa, concurrente o posterior a su aparición, como la enfermedad inflamatoria intestinal (colitis ulcerativa, enfermedad de Crohn, 20-30%), poliartritis (20%), trastornos hematológicos (leucemia mieloide aguda y crónica, tricoleucemia, mielodisplasia, gammapatía monoclonal IgA) (15-25%), puede ser una manifestación cutánea de enfermedades autoinflamatorias monogénicas, como el síndrome PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and suppurative hidradenitis) o PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis) o aparecer como acompañante de una dermatosis pustulosa subcórnea, enfermedad de Behçet o del síndrome de Sweet; raramente se debe a medicamentos. La metodología utilizada para el presente trabajo de investigación, se enfoca hacia una metodología orientada hacia la necesidad de indagar en forma precisa y coherente una situación. Enmarcada dentro de una revisión bibliográfica de tipo documental, ya que nos vamos a ocupar de temas planteados a nivel teórico como es Pioderma gangrenoso. La técnica para la recolección de datos está constituida por materiales impresos, audiovisuales y electrónicos, estos últimos como Google Académico, PubMed, entre otros. La información aquí obtenida será revisada para su posterior análisis. En base a los casos aquí presentados, se confirma lo analizado en la literatura revisada, que los casos de piodermas gangrenosos, se controlan con farmacología, específicamente con corticoesteroides, analgésicos y desinflamatorios, que en la mayoría de los casos evolucionan favorablemente. Otro punto a considerar es que también se prueba que otras patologías o comorbilidades que pueda tener un paciente, pueden desencadenar procedimientos que terminen en piodermas gangrenosos, en uno de los casos clínicos aquí presentados uno de los pacientes presento lesión ulcerada probablemente como consecuencia de la diabetes mellitus que padece desde hace mucho tiempo, en otros casos es posible la generación de esta patología como enfermedades de Crohn, leucemia, artritis reumatoide, entre otras.

Case Report: Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne: A Single-Center Experience and Literature Review

ObjectivesThis study aims to describe the characteristics of patients diagnosed with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome at a single center in China and provide an up-to-date literature review.MethodsThe clinical data and genotype of three Chinese Han patients were carefully documented and studied. We also conducted a systematic literature review on PAPA syndrome.ResultsA total of three patients were diagnosed with PAPA syndrome at our center from 2018 to 2020. Arthritis was observed in all three patients, while pyoderma gangrenosum (PG) was found in two patients and acne in one patient. Other manifestations included pathergy reaction, intermittent fever, oral ulcer, keratitis, proteinuria, and hematuria. The PSTPIP1 A230T mutation was identified in two patients, and a novel Y119C variation was revealed in a sporadic patient. A total of 76 patients with PAPA syndrome reported in 29 articles were included in our literature review. The classical triad of arthritis, PG, and acne was visible in only 16 (25.4%) patients, while 24 (38.1%) exhibited only one major symptom. Skin lesions were more commonly seen in patients with adult-onset disease than those with childhood-onset disease (100 vs. 83%), whereas arthritis was less common (50 vs. 98.1%). Steroid and/or biological agents were effective in most patients.ConclusionsThe rarity and phenotypic heterogeneity associated with PAPA syndrome make the diagnosis a huge challenge to physicians, especially in adult patients. A significant portion of patients did not exhibit the full spectrum of the classical triad. Accordingly, gene testing is critically helpful for diagnosis.

Clinical and genetic characteristics of PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome

Objective To summarise the clinical and genetic characteristics of three children with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. Methods This study retrospectively analysed the clinical and genetic data of three children with PAMI syndrome in our hospital between April 2018 and January 2020. Results One male and two female children were 6 years and 5 months, 8 years and 7 months, and 13 years and 3 months of age. All three patients had a recurrent blood trilineage hypoplasia and splenomegaly. Patient 1 had pyoderma gangrenosum, and Ludwig’s angina. Patient 2 had pyogenic arthritis, and pyoderma gangrenosum. Patient 3 had hepatomegaly, pyogenic arthritis, and pulmonary hypertension. Laboratory tests revealed that all three children had elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patient 1: C-antineutrophilic cytoplasmic antibodies(c-ANCA), positive; antiglobulin test (Coombs), positive. Patient 2: blood zinc, 4.38 mg/L (elevated). Patient 3: Antinuclear antibodies (ANA), 1:100, β2 glycoprotein I, positive; Coombs test, positive; RF, 28.3 U/ml (elevated); C3, 0.77 g/L (decreased). Genetic testing showed that all 3 patients had PSTPIP1 c.748G > A (p.E250K) spontaneous heterozygous mutations, suggesting the diagnosis of PAMI syndrome. Patient 1 was treated with a combination of methylprednisolone and cyclosporine for 8 months. The patient did not develop new skin lesions. The blood count showed mild neutropenia. The spleen was considerably retracted and the CRP became normal. Patient 2 was treated with etanercept and methylprednisolone. The patient had no further arthralgias and pyoderma gangrenosum showed improvement. The spleen was smaller than before. White blood cells were shown to be approximately 2–3 × 109/L. The haematocrit, platelets, CRP, and AESR were normal. Patient 3 was treated with methylprednisolone, methotrexate, and infliximab 4 times. The patient’s joint symptoms disappeared gradually and the liver retracted markedly. The pulmonary artery pressure returned to normal. Moreover, Coombs test result was negative. CRP and AESR were lower than before. Conclusion PAMI syndrome can manifest as pyogenic arthritis, pyoderma gangrenosum, acne, and trilineage hypoplasia, as well as autoimmune diseases. Glucocorticoid and immunosuppressive therapy are partially effective and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing is helpful to confirm diagnosis.

Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab

Syndromic hidradenitis suppurativa (HS) is a form of symptom constellations, which differs from the familial and genetic form and comprises predominantly osteoarticular manifestations. Many forms include pyoderma gangrenosum and acne (PASH), pyogenic arthritis (PAPASH), spondyloarthritis (PASS) and psoriatic arthritis (PsAPASH) and are categorized in the autoinflammatory syndromes. Anti-TNF-α and anti-IL-1a blockade are between the therapeutic approaches that improve skin symptoms and prevent permanent osteoarticular damage. This case report refers to the successful treatment of a mixed phenotype of the aforementioned symptoms using the IL-17A inhibitor secukinumab after initial treatment with adalimumab. The therapy improved both cutaneous and reported osteoarticular symptoms. Different approaches for these recalcitrant HS syndromes are essential in order to achieve long-term remission for those patients.

Tuberculosis of bilateral ankles: Misdiagnosed as rheumatoid arthritis

The osteoarticular tuberculosis is a uncommon diease, which is accout for 0.1%-0.3% of Tuberculosis (TB). The involoment of foot and ankle is only 0.01%-0.03% of TB, particularly the bilateral feet and ankles are affected is extremely rare. Futhermore, its clinical manifestation is atypical and similar with autoimmune disorder, subacute or chronic pyogenic arthritis, osteochondrosis, benign bone tumors and so on, which conduce to the delay of its diagnose and therapy along with unfavourable prognosis. Here we present a case of a 52-year-old man with bilateral feet and ankles tuberculous arthritis, misdiagnosed successively Rheumatoid Arthritis (RA) and Poncet’s diease. It is hope that can enhance the alertness about osteoarticular tuberculosis. Keywords: Osteoarticular tuberculosis; ankle; foot; misdignose.