Acne Syndrome Research Articles

Skin rash and arthritis a simplified appraisal of less common associations

Skin and joint manifestations are part of the clinical spectrum of many disorders. Well-known associations include psoriatic arthritis and arthritis associated with autoimmune connective tissue diseases. This review focuses on less common associations where skin lesions can provide easily accessible and valuable diagnostic clues, and directly lead to the specific diagnosis or limit the list of possibilities. This may also affect health care resources as diagnostic tests are often low-specific, highly expensive and poorly available. This group of diseases can be divided into two subsets, based on the presence/absence of fever, and then further classified according to elementary skin lesions (macular, urticarial, maculo-papular, vesico-bullous, pustular, petechial and nodular). In most instances joint involvement occurs as peripheral migrating polyarthritis. Erythematosus macular or urticarial rashes occur in most febrile disorders such as monogenic autoinflammatory syndromes, Schnitzler's syndrome, Still's disease and rheumatic fever and afebrile diseases as urticarial vasculitis. Pustular rash may be observed in chronic recurrent multifocal osteomyelitis (CRMO) and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA) syndrome (both febrile) as well as in Behcet's disease and Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome (both non-febrile). Papular lesions are typical of secondary syphilis, sarcoidosis, interstitial granulomatous dermatitis, papular petechial of cutaneous small-vessel vasculitis and nodular lesions of polyarteritis nodosa and multicentric reticulohistiocytosis all of which are afebrile. Differential diagnosis includes infections and drug reactions which may mimic several of these conditions. To biopsy the right skin lesion at the right time it is essential to obtain relevant histological information.

FRI0026 Evidence for interleukin (IL)-1β pathway activation in monocytes from patients with familial mediterranean fever (fmf) and pyogenic sterile arthritis, pyoderma gangrenosum and acne (papa) syndrome

BackgroundFamilial Mediterranean fever (FMF) and Pyogenic Arthritis, Pyoderma gangrenosum and Acne (PAPA) syndrome are autoinflammatory disorders that are thought to share similar pathoetiology. While FMF is due to mutations of...

SP0156 What’s new in clinical management of autoinflammatory diseases

Under the term of monogenic autoinflammatory syndromes are gathered a number of different conditions secondary to mutations of genes coding for proteins that play a pivotal role in the regulation...

AB1179 Failure of adalimumab treatment in three patients with papa syndrome

BackgroundPyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare autosomal dominant autoinflammatory disorder due to mutations in the CD2 binding protein 1 (CD2BP1) gene. This syndrome is...

OP0024 The Function of PSTPIP1 and S100A8/S100A9 in Hyperzincaemia & Hypercalprotectinaemia and the PAPA-Syndrom

BackgroundHypercalprotectinaemia and hyperzincaemia is a very rare autoinflammatory syndrome that is characterized by excessively high S100A8/S100A9 complex (calprotectin) serum concentrations (0.9-12.0 g/l, normal range < 0.001 g/l) not present in...

A sporadic case of pyogenic arthritis, pyoderma gangrenosum and acne syndrome without an identifiable mutation

A sporadic case of pyogenic arthritis, pyoderma gangrenosum and acne syndrome without an identifiable mutation

Monogenic autoinflammatory diseases: concept and clinical manifestations.

The objective of this review is to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary "periodic fever syndromes", familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) and 6. very rare conditions presenting with autoinflammation and immunodeficiency.

Inflammation in Mice Ectopically Expressing Human Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome-associated PSTPIP1 A230T Mutant Proteins

Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome (PAPA syndrome) is an autoinflammatory disease caused by aberrant production of the proinflammatory cytokine interleukin-1. Mutations in the gene encoding proline serine threonine phosphatase-interacting protein-1 (PSTPIP1) have been linked to PAPA syndrome. PSTPIP1 is an adaptor protein that interacts with PYRIN, the protein encoded by the Mediterranean Fever (MEFV) gene whose mutations cause Familial Mediterranean Fever (FMF). However, the pathophysiological function of PSTPIP1 remains to be elucidated. We have generated mouse strains that either are PSTPIP1 deficient or ectopically express mutant PSTPIP1. Results from analyzing these mice suggested that PSTPIP1 is not an essential regulator of the Nlrp3, Aim2, or Nlrc4 inflammasomes. Although common features of human PAPA syndrome such as pyogenic arthritis and skin inflammation were not recapitulated in the mouse model, ectopic expression of the mutant but not the wild type PSTPIP1 in mice lead to partial embryonic lethality, growth retardation, and elevated level of circulating proinflammatory cytokines.

Identification of a Homozygous PSTPIP1 Mutation in a Patient With a PAPA-Like Syndrome Responding to Canakinumab Treatment

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome (OMIM 604416) is a rare autosomal dominant inherited autoinflammatory syndrome characterized by pyogenic sterile arthritis and less frequently accompanied by pyoderma gangrenosum and acne. It is associated with dominant missense mutations in the proline-serine-threonine phosphatase-interacting protein 1 gene (PSTPIP1) located on chromosome 15. The patient was diagnosed as having features of a PAPA-like syndrome in which cutaneous manifestations, such as pyoderma gangrenosum and acne fulminans, predominated. Sequencing of the PSTPIP1 gene was performed in the patient and his extended family. The patient's DNA analysis revealed a homozygous nucleotide exchange c.773G>C in the PSTPIP1 gene, leading to the substitution of glycine 258 by alanine (p.Gly258Ala), a previously reported heterozygous polymorphism. Heterozygous changes were identified in both of the patient's parents and in 7 other family members, all of whom were asymptomatic. The patient was treated with canakinumab, a human anti-interleukin 1β monoclonal antibody, which led to rapid remission of the symptoms. To our knowledge, this is the first reported case of the resolution of dermatological symptoms associated with a PAPA-like syndrome using canakinumab treatment. Further study of the p.Gly258Ala variant is warranted to determine whether this mutation has a role in causing an apparently recessive cutaneous syndrome resembling PAPA syndrome.

A Case of Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne(PAPA) Syndrome Accompanied by Nephrosclerosis, Splenomegaly and Intestinal Lesions

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autosomal dominant autoinflammatory disorder, caused by a missense mutation in the PSTPIP1 gene. Cutaneous and articular manifestations are characteristic but little is known about organ involvement of this disorder. Here, we describe the case of a patient with PAPA syndrome who was admitted to our hospital for evaluation of proteinuria. He had a history of recurrent abdominal attacks with lesions resembling Crohn’s disease. A renal biopsy revealed nephrosclerosis, which was presumed to be due to a long history of systemic inflammation. He also showed marked splenomegaly with pancytopenia. These manifestations should be kept in mind during the follow up of this syndrome.

Autoinflammatory Syndromes

The autoinflammatory syndromes are a group of diseases characterized by apparently spontaneous episodes of fever and inflammatory manifestations in several organs. Some of these conditions, such as familial Mediterranean fever (FMF), have been known for over a century, but others have only recently been defined. The discovery of the genetic defects underlying the pathophysiology of these diseases has been critical for their understanding and eventual grouping in a new category of diseases. Despite their rarity, the monogenic autoinflammatory syndromes are relevant because identification of the causative genetic variants has greatly expanded our understanding of the inflammatory process and the innate immune system and defined new diseases and their treatment. In addition, the autoinflammatory syndromes have been incorporated in the differential diagnosis of fever of unknown origin. In this chapter, the following selected syndromes are reviewed: FMF; cryopyrin-associated periodic syndromes; tumor necrosis factor–associated periodic fever syndrome; hyper-IgD syndrome; pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome; Blau syndrome; deficiency of the interleukin-1 receptor antagonist; Majeed syndrome; cherubism; joint contractures, muscular atrophy, macrocytic anemia, and panniculitis-associated lipodystrophy (JMP) syndrome; CANDLE syndrome; systemic-onset juvenile idiopathic arthritis; and adult-onset Still disease. Each syndrome is broken down by epidemiology, etiology, pathogenesis, diagnosis, differential diagnosis, management, complications, and prognosis. This review contains 4 highly rendered figures, 5 tables, and 96 references.

Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review

ObjectiveTo evaluate the response to treatment of autoinflammatory diseases from an international registry and an up-to-date literature review.MethodsThe response to treatment was studied in a web-based registry in which clinical...

Ostéomyélite sclérosante diffuse de la mandibule et SAPHO

Diffuse sclerosing osteomyelitis of the mandible may be the presenting manifestation of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. We report an additional case of such a presentation.

Rare hereditary autoinflammatory disorders: Towards an understanding of critical in vivo inflammatory pathways

Hereditary autoinflammatory syndromes are monogenic disorders with an inborn error of innate immunity, and include periodic fever syndromes such as familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome and cryopyrin-associated periodic syndromes (CAPS), pyogenic diseases such as pyogenic arthritis, pyoderma gangrenosum and acne syndrome (PAPAS), and granulomatous diseases such as Blau syndrome. By identifying the genetic abnormalities and subsequent analyses of the molecular mechanisms underlying these disorders, several critical in vivo pathways for inflammatory processes have been discovered. In this review, three categories of autoinflammatory disorders are discussed: inflammasomopathies, receptor antagonist deficiencies and proteasome disability syndromes. Inflammasomopathies are diseases with dysregulated NLRP3 inflammasome activation, and include CAPS with NLRP3, FMF with MEFV, and PAPAS with PSTPIP1 mutations. Analyses of these diseases have clarified some critical pathways regulating NLRP3 inflammasome signaling. Receptor antagonist deficiencies include the newly defined deficiency for interleukin-1 receptor antagonist resulting in sterile multifocal osteomyelitis with periostosis and pustulosis, and deficiency for interleukin-36 receptor antagonist resulting in generalized pustular psoriasis. The identification of these genetic abnormalities has revealed a critical role for receptor antagonists of IL-1 family cytokines in regulating neutrophil activation/recruitment. Finally, proteasome disability syndromes with PSMB8 mutations include Nakajo-Nishimura syndrome and related disorders distributed globally. Analyses of these diseases have unexpectedly shown a critical role of the ubiquitin-proteasome system in the regulation or homeostasis of inflammation/metabolism. Since there still remain a number of predicted but undefined hereditary autoinflammatory syndromes, further clinical and genetic approaches are required to discover novel in vivo critical inflammatory pathways.

Chronic refractory osteomyelitis as a part of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: a diagnostic challenge

Chronic refractory osteomyelitis as a part of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: a diagnostic challenge

The SAPHO syndrome – Are microbes involved?

The syndrome of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) includes a rare group of chronic, relapsing, inflammatory osteoarticular disorders that is conventionally associated with manifestations in the skin. Diagnostic dilemmas can arise due to incomplete manifestations or confusion generated through mimicking of other conditions, such as osteomyelitis. The aetiology of this syndrome remains unclear, but probably involves genetic, immunological and infectious mechanisms. The possible pathogenetic role of infectious agents in genetically predisposed individuals, resulting in a 'reactive osteitis', has been suggested because microbes such as Propionibacterium acnes have been recovered from bone biopsy samples. However, this hypothesis has not been demonstrated as yet. Current knowledge with regard to treatment of this syndrome is based on results reported from small case studies and, thus, is still empiric. The use of antibiotics, instituted based on the isolation of Propionibacterium acnes, has been reported to show conflicting results. Promising results for potential future application have recently been reported for treatment of SAPHO with bisphosphonates and antagonists of tumour necrosis factor-α. This review aims to evaluate the existing knowledge on the SAPHO syndrome and to provide information on symptoms, diagnosis and treatment options for this disease.

Autoinflammatory diseases - a new entity of inflammation

The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells. The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes. NLRP3 inflammasome activation and IL-1β secretion have recently emerged as a central mechanism in the pathogenesis of disease. Here we describe four genetically defined syndromes like cryopyrin-associated periodic syndromes (CAPS, cryopyrinopathies), mevalonate kinase deficiency (MKD) or hyper-IgD and periodic fever syndrome (HIDS), pyogenic aseptic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome), and deficiency of interleukin-1-receptor antagonist (DIRA) along with the pitfall for understanding the pathphysiology.

Autoinflammatory diseases and the inflammasome: mechanisms of IL-1β activation leading to neutrophil-rich skin disorders

Autoinflammatory diseases were initially assigned to the hereditary recurrent fevers that were characterized by unprovoked episodes of inflammation without antigen-specific T cells or high titers of auto-antibodies, in contrast to the autoimmune diseases in which acquired immunity played an essential role. Except for Blau syndrome and early-onset sarcoidosis that are associated with granuloma due to NOD2 mutations and classified as NF-κB activation disorders, the major types of autoinflammatory diseases are defined as IL-1β activating disorders or inflammasomopathies. This is based on accumulating evidence for the efficacy of anti-IL-1 therapy. These diseases include intrinsic cryopyrin-associated periodic syndrome (CAPS), extrinsic familial Mediterranean fever, hyper IgD syndrome, pyogenic sterile arthritis pyoderma gangrenosum and acne syndrome, and deficiency of an IL-1 receptor antagonist. Knowledge obtained from these autoinflammatory disorders should also be pertinent to a number of common disorders. For example, neutrophil migration is observed in autoinflammatory CAPS and common inflammatory keratoses represented by psoriasis. Abnormal regulation of the innate immune response and Th17 cell differentiation via IL-1 signaling may be associated with the molecular pathogenesis of these conditions.

Mutations in IL1RN in bone and skin inflammation

Autoinflammatory diseases are a group of disorders characterized by seemingly unprovoked inflammation in the absence of high-titer autoantibodies or antigen-specific T cells. They include familial Mediterranean fever; the tumor necrosis factor receptor–associated periodic syndrome; the hyper-IgD syndrome; a syndrome of pyogenic arthritis, pyoderma gangrenosum and acne; the cryopyrin-associated periodic syndromes; chronic recurrent multifocal osteomyelitis and others. A new autoinflammatory syndrome of skin and bone caused by recessive mutations in IL1RN, the gene encoding the interleukin-1–receptor antagonist, has been recently described and has been named deficiency of the interleukin-1-receptor antagonist, or DIRA. Three unrelated patients with symptoms suggestive of DIRA were referred to our laboratory. The three patients had skin and bone inflammation since birth manifested as pustulosis and chronic recurrent multifocal osteomyelitis. The course of the disease was progressive with chronic sequelae. Two patients were from Brazil and the third is from Palestine. We identified a novel homozygous inframe deletion of 15 bases (c.213-228delAGATGTGGTACCCAT; p.72-77delDVVPI) in the two unrelated patients from Brazil. In the Palestinian patient, a homozygous nonsense mutation (c.160C&gt;T; p.Q54X) was identified. This mutation has been described before in a family from Lebanon, which probably reflects on a founder effect in Middle Eastern populations.

Pediatric hereditary autoinflammatory syndromes

To describe the most prevalent pediatric hereditary autoinflammatory syndromes. A review of the literature including relevant references from the PubMed and SciELO was carried out using the keywords autoinflammatory syndromes and child. The hereditary autoinflammatory syndromes are caused by monogenic defects of innate immunity and are classified as primary immunodeficiencies. These syndromes are characterized by recurrent or persistent systemic inflammatory symptoms and must be distinguished from infectious diseases, autoimmune diseases, and other primary immunodeficiencies. This review describes the epidemiological, clinical and laboratory features, prognosis, and treatment of the main autoinflammatory syndromes, namely: familial Mediterranean fever; TNF receptor associated periodic syndrome; the cryopyrinopathies; mevalonate kinase deficiency; pediatric granulomatous arthritis; pyogenic arthritis, pyoderma gangrenosum and acne syndrome; Majeed syndrome; and deficiency of interleukin 1 receptor antagonist. The cryopyrinopathies discussed include neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic, cutaneous and articular syndrome), Muckle-Wells syndrome, and familial cold autoinflammatory syndrome. Pediatricians must recognize the clinical features of the most prevalent autoinflammatory syndromes. Early referral to a pediatric rheumatologist may allow early diagnosis and institution of treatment, with improvement in the quality of life of these patients.