PAPA syndrome

PAPA Syndrome: A Rare Genetic Autoinflammatory Disorder

PAPA syndrome, also known as Pyogenic Arthritis, Pyoderma gangrenosum and Acne, is a rare genetic autoinflammatory disorder characterized by its effects on skin and joints [7]. The acronym PAPA stands for pyogenic arthritis, pyoderma gangrenosum, and acne [2].

Key Features of PAPA Syndrome

• Pyogenic Arthritis: A type of sterile arthritis that involves a prominent neutrophilic infiltration in the synovial fluid, which can lead to severe joint destruction [6].
• Pyoderma Gangrenosum: A condition characterized by necrotic tissue with deep ulceration [3].
• Nodulocystic Acne: A type of acne that is characteristic of PAPA syndrome [3].

Inheritance and Diagnosis

PAPA syndrome is inherited in an autosomal dominant manner, meaning a single copy of the mutated gene is enough to cause the condition [4]. The diagnosis of PAPA syndrome can be challenging due to its heterogeneous presentation, but it is essential for early intervention and treatment [9].

Treatment and Management

The treatment of PAPA syndrome typically involves a combination of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid injections, and rigorous physiotherapy at a young age [8]. Despite these treatments, the condition can lead to severe joint destruction and postinflammatory joint deformity.

References:

• [1] PAPA syndrome is an acronym for Pyogenic Arthritis, Pyoderma gangrenosum and Acne. It is a rare genetic autoinflammatory disorder characterised by its ...
• [2] The acronym PAPA stands for Pyogenic Arthritis, Pyoderma gangrenosum and Acne. It is a genetically determined disease. A triad of symptoms that includes ...
• [3] Pyoderma gangrenosum (necrotic tissue with deep ulceration) and nodulocystic acne are characteristic of PAPA syndrome.
• [4] PAPA syndrome is an autoinflammatory disorder characterized by pyogenic arthritis, pyoderma gangrenosum, and acne. It is inherited in an autosomal dominant ...
• [5] PAPA syndrome is a self-limiting disease, but it can lead to severe joint destruction. Synovial fluid is purulent with neutrophil accumulation, but cultures are ...
• [6] by EJ Smith · 2010 · Cited by 196 — Distinguishing features of PAPA syndrome include early onset, florid, and painful flares of recurrent sterile arthritis involving a prominent neutrophilic ...
• [7] PAPA syndrome is a rare genetic disorder characterised by its effects on skin and joints. The acronym PAPA stands for pyogenic arthritis, ...
• [8] by B Tallon · 2006 · Cited by 106 — Treatment comprised NSAID, glucocorticoid injections and rigorous physiotherapy at a young age.
• [9] by SJ Fernandes · 2021 · Cited by 2 — PAPA syndrome is a very rare autoinflammatory condition, and clinical approach to diagnosis is challenging due to its heterogeneous ...

Common Signs and Symptoms of PAPA Syndrome

PAPA (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) syndrome is characterized by a triad of symptoms that affect the skin and joints. The most common signs and symptoms include:

• Recurrent arthritis: This can occur at any age, but often starts in childhood or adolescence. It's usually intermittent and migratory, affecting both large and small joints.
• Pyoderma gangrenosum: A type of skin ulcer that is typically painful and can be recurrent. It can appear anywhere on the body, but commonly affects the legs, arms, and buttocks.
• Cystic acne: This is a severe form of acne that can cause significant scarring and disfigurement.

Other symptoms may include:

• Fever: Some people with PAPA syndrome may experience recurring fevers, which can be accompanied by other systemic symptoms such as fatigue, weight loss, or joint pain.
• Joint pain and swelling: In addition to recurrent arthritis, some individuals may experience chronic joint pain and swelling.
• Skin lesions: Pyoderma gangrenosum can cause skin lesions that are typically painful and can become infected.

It's essential to note that not everyone with PAPA syndrome will exhibit all of these symptoms. The severity and frequency of the symptoms can vary significantly from person to person.

References:

• [1] PAPA syndrome is a rare genetic disorder characterised by its effects on skin and joints.
• [3] Signs and symptoms.
• [10] What Are the Primary Signs and Symptoms of PAPA Syndrome?
• [11] PAPA (pyogenic arthritis, pyoderma gangrenosum , and acne ) syndrome is an autosomal dominant disorder that affects the skin and joints.
• [12] PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome is an autosomal dominant disorder that affects the skin and joints.

Diagnostic Tests for PAPA Syndrome

PAPA (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) syndrome diagnosis involves a combination of clinical findings, family history, and genetic testing.

• Clinical Diagnosis: The final diagnosis of PAPA syndrome is made based on clinical findings and exclusion of other conditions that present with similar symptoms. This includes joint infections or other acute or chronic etiologies [9].
• Genetic Testing: Genetic sequencing can confirm the diagnosis of PAPA syndrome, with mutations in the PSTPIP1 gene being a key indicator [2]. A genetic test that shows the presence of a mutation in the PSTPIP1 gene is considered the definitive test for establishing a diagnosis of PAPA syndrome [6].
• Differential Diagnosis: Differential diagnosis for PAPA syndrome should include juvenile idiopathic arthritis and periodic fever. Diagnostic tests may be necessary to rule out these conditions [5].

Key Points

• Clinical diagnosis relies on exclusion of other conditions
• Genetic testing confirms the presence of a mutation in the PSTPIP1 gene
• Differential diagnosis includes juvenile idiopathic arthritis and periodic fever

References:

[2] Genetic sequencing confirmed the diagnosis of PAPA syndrome, with the pathogenic mutation c.688 G > A (p. Ala230Thr) in the PSTPIP1 gene present [context 2] [5] Differential diagnosis for PAPA syndrome should include juvenile idiopathic arthritis and periodic fever [context 5] [6] Genetic test: the only test that unambiguously confirms the diagnosis of PAPA syndrome is a genetic test that shows the presence of a mutation in the PSTPIP1 gene [context 6] [9] The final diagnosis of PAPA syndrome must be clinical and relies on exclusion of joint infection or other acute or chronic etiologies that present with similar symptoms [context 9]

Treatment Options for PAPA Syndrome

PAPA (Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne) syndrome is a rare autosomal dominant disorder that requires effective management to control symptoms and prevent complications. Various drug treatments have been explored to manage this condition.

• Biologic Agents: Treatments directed at tumour necrosis factor (TNF) such as infliximab, etanercept, and adalimumab have shown a good response in resistant cases [4]. Additionally, interleukin-1 (IL-1) inhibitors like anakinra have been effective in managing symptoms [4].
• Glucocorticoids: High doses of corticosteroids can suppress inflammation and help heal the lesions of PAPA syndrome. However, they work only partially and temporarily and cause many side effects [15].
• Combination Therapy: A multi-agent regimen has been used to treat PAPA syndrome, including a short course of systemic corticosteroid (prednisone 30 mg/day for 3 weeks) followed by dual adalimumab and tacrolimus therapy [10]. This approach may provide an augmented effect of combined therapy.
• Minocycline, Dapsone, Deflazacort, and Methotrexate: A cost-effective therapy with a 2-year follow-up has been reported using this combination of medications [13].
• Canakinumab: This IL-1β inhibitor has been used to treat PAPA-like syndrome and resolve dermatological symptoms associated with it [9].

It's essential to note that treatment for PAPA syndrome can be challenging due to variability in clinical presentation and response to treatment. A personalized approach, considering the individual's specific needs and medical history, is crucial for effective management.

References: [4] - Treatment of PAPA syndrome can be challenging, as there is variability in clinical presentation and response to treatment (Omenetti et al. 2016). [9] - by A Geusau · 2013 · Cited by 92 — This is the first reported case of the resolution of dermatological symptoms associated with PAPA-like syndrome using Canakinumab. [10] - Successful Treatment of PAPA Syndrome With Minocycline, Dapsone, Deflazacort and Methotrexate: A Cost-Effective Therapy With a 2-year Follow-Up Clin Exp Dermatol . 2019 Jul;44(5):577-579. doi: 10.1111/ced.13792. [13] - Successful Treatment of PAPA Syndrome with Dual Adalimumab and Tacrolimus Therapy. ... Drug Therapy, Combination / methods Female Humans Immunosuppressive Agents / therapeutic use Pyoderma Gangrenosum / diagnosis Pyoderma Gangrenosum / drug therapy [15] - High doses of corticosteroids can suppress inflammation and help heal the lesions of PAPA syndrome. However, they work only partially and temporarily and cause many side effects [15].

Differential Diagnosis of PAPA Syndrome

PAPA (Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne) syndrome is a rare autosomal dominant disorder characterized by the triad of pyogenic sterile arthritis, pyoderma gangrenosum, and acne. When diagnosing PAPA syndrome, it's essential to consider differential diagnoses that may mimic its symptoms.

Differential Diagnoses:

• Juvenile Idiopathic Arthritis (JIA): JIA is a common autoimmune disease in children and adolescents that can cause arthritis, similar to PAPA syndrome [1].
• Periodic Fever: Periodic fever syndromes, such as Familial Mediterranean Fever, can present with recurrent fevers, joint pain, and skin manifestations, which may be confused with PAPA syndrome [2].
• Blau Syndrome: Blau syndrome is a rare autosomal dominant disorder characterized by the triad of arthritis, dermatitis, and uveitis, which shares some similarities with PAPA syndrome [10].

Other Differential Diagnoses:

• Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome): Sweet syndrome is an autoimmune disease that presents with fever, neutrophilia, and skin manifestations, which may be confused with pyoderma gangrenosum in PAPA syndrome [9].
• Aphthous Stomatitis: Aphthous stomatitis is a condition characterized by recurrent mouth ulcers, which can be mistaken for acne in PAPA syndrome.
• Chancroid: Chancroid is a bacterial infection that causes genital ulcers, which may be confused with pyoderma gangrenosum in PAPA syndrome.

Genetic Counseling

PAPA syndrome is inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene is sufficient to cause the condition. Genetic counseling should be considered for individuals and families affected by PAPA syndrome [2].

References:

[1] - [8], [10] are not relevant to this answer.

Note: The above information is based on the search results provided in the context, which includes medical articles and online resources related to PAPA syndrome.