proteosome-associated autoinflammatory syndrome 2

Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is a rare genetic disorder characterized by early-onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and variable immunodeficiency [3][4]. It is an autosomal dominant disorder, meaning that only one copy of the mutated gene is needed to cause the condition [3][5].

The clinical features of PRAAS2 include:

• Abnormality of blood and blood-forming tissues (thrombocytopenia)
• Abnormality of head or neck (periorbital edema)
• Abnormality of limbs

PRAAS2 is characterized by severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency [6]. This syndrome is part of a group of genetic disorders known as proteasome-associated autoinflammatory syndromes.

The symptoms of PRAAS2 typically begin in early infancy and can include skin eruptions, recurrent fever, joint inflammation, and other systemic manifestations [7][8].

References:

[3] Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is an autosomal dominant disorder with onset in early infancy. [4] Affected individuals develop severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency. This syndrome is part of a group of genetic disorders known as proteasome-associated autoinflammatory syndromes. [5] Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is characterized by early onset combined immunodeficiency, inflammatory neutrophilic dermatosis, and variable immunodeficiency. [6] It is characterized by severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency. This syndrome is part of a group of genetic disorders known as proteasome-associated autoinflammatory syndromes. [7] Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is an autosomal dominant disorder with onset in early infancy. Affected individuals develop ... [8] by JJ Papendorf · 2023 · Cited by 13 — Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers typically cause recurring autoinflammation referred to ...

Signs and Symptoms of Proteasome-Associated Autoinflammatory Syndrome 2

Proteasome-Associated Autoinflammatory Syndrome 2 (PAAS2) is a rare genetic disorder characterized by severe inflammatory symptoms. The signs and symptoms of PAAS2 can vary from person to person, but they often include:

• Recurrent episodes of fever: This is one of the most common symptoms of PAAS2, with affected individuals experiencing repeated episodes of high fever [8].
• Growth retardation: Children with PAAS2 may experience delayed growth and development due to chronic inflammation and recurrent infections [8].
• Facial edema: Swelling around the eyes and face is a common symptom of PAAS2, which can be accompanied by periorbital edema (swelling around the eyes) [8].
• Periorbital edema: This symptom is often associated with facial edema and can be a sign of underlying inflammation [3].
• Recurring skin rashes: Affected individuals may experience recurring episodes of skin rashes, which can be annular, nodular, or maculopapular in nature [1].
• Abdominal or chest pain: Some people with PAAS2 may experience recurrent episodes of abdominal or chest pain due to inflammation and infection [9].
• Lymphadenopathy: Enlarged lymph nodes are a common symptom of PAAS2, which can be accompanied by fever and other systemic symptoms [9].

These symptoms can vary in severity and frequency from person to person, but they often require prompt medical attention to manage and prevent long-term complications.

References: [1] - Context result 1 [8] - Context result 8 [3] - Context result 3 [9] - Context result 9

Diagnostic Tests for Proteasome-associated Autoinflammatory Syndrome 2 (PRAAS2)

Proteasome-associated autoinflammatory syndrome 2 (PRAAS2) is a rare genetic disorder characterized by severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency. Diagnosing PRAAS2 can be challenging, but several diagnostic tests are available to confirm the condition.

• Genetic Testing: Genetic testing is considered the gold standard for diagnosing PRAAS2. This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 117 genes associated with autoinflammatory disorders [4]. A genetic test can identify mutations in the PSMB8 gene, which is responsible for PRAAS2.
• Proteasomal Activity Testing: Proteasomal activity testing may serve as a useful tool for the diagnosis of PRAAS2 in suspicious cases [6][9]. This test measures the activity of proteasomes, which are complexes that break down proteins in cells. Abnormal proteasomal activity can be indicative of PRAAS2.
• Histopathologic Examination: Histopathologic examination of skin biopsy samples may reveal focal inflammatory changes, which can support a diagnosis of PRAAS2 [1].
• Clinical Presentation and Family History: A thorough clinical presentation and family history are essential for diagnosing PRAAS2. The condition is characterized by severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency [5].

References:

[1] Context 1 [4] Context 4 [5] Context 5 [6] Context 6 [9] Context 9

Treatment Options for Proteasome-Associated Autoinflammatory Syndrome 2 (PRAAS2)

Proteasome-associated autoinflammatory syndrome 2 (PRAAS2) is a rare genetic disorder characterized by recurrent episodes of inflammation. While there are no specific treatments approved for PRAAS2, various medications have been used to manage symptoms and prevent flares.

• Janus Kinase Inhibitors: These medications, such as baricitinib, have been shown to be effective in reducing inflammation and preventing disease flares [3][4]. However, dose reductions may lead to disease flares and rebound inflammation [4].
• Tofacitinib: This Janus kinase inhibitor has resulted in disease remission in some cases [5].
• Immunosuppressive Drugs: Lifelong immunosuppressive therapy may be necessary for some individuals with PRAAS2, although the efficacy of these medications can vary [3][6].

Other Treatment Considerations

• Dapsone: This medication has been used to treat various immune-mediated conditions and may have a role in managing symptoms associated with PRAAS2 [7].
• Biologics: Targeting interleukin-1 and tumor necrosis factor with biologics, such as those mentioned in [2], may also be considered for treatment.

Important Note

It is essential to consult with a healthcare professional for personalized medical advice and treatment. They can help determine the best course of action based on individual circumstances.

References:

[1] McDermott A (2015) Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. [2] Du Y (2023) Review of biologics for treating proteasome disorders. [3] Verhoeven D (2022) Treatment options for proteasome disorders. [4] Gedik KC (2024) Disease flares and rebound inflammation with baricitinib dose reductions. [5] Proteasome-associated autoinflammatory syndrome 2; PRAAS2; digenic inheritance. [6] Verhoeven D (2022) Treatment options for proteasome disorders. [7] Soriano A (2020) Dapsone in the treatment of immune-mediated conditions.

The differential diagnosis for Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) includes several conditions that can present with similar symptoms.

• Sweet's syndrome, a rare skin condition characterized by fever and rash [4]
• Erythema nodosum, an inflammatory condition of the skin that can cause red, painful lesions [4]
• Juvenile dermatomyositis, a type of arthritis that affects children and young adults, causing muscle weakness and skin rashes [4]
• Cryopyrin-associated periodic syndromes (CAPS), a group of rare genetic disorders that can cause recurring episodes of fever, rash, and joint pain [8]

It's worth noting that the differential diagnosis for PRAAS2 is not as well established as it is for other proteasome-associated autoinflammatory syndromes, such as Proteasome-associated autoinflammatory syndrome-1 (PRAAS1) [3]. However, these conditions should be considered in the differential diagnosis of PRAAS2.

References: [4] - The differential diagnosis of PRAAS patients includes Sweet's syndrome, erythema nodosum, juvenile dermatomyositis, cryopyrin-associated periodic syndromes (CAPS), and other autoinflammatory disorders. [5] [8] - Other differential diagnoses are systemic lupus erythematosus and other autoinflammatory syndromes such as cryopyrin-associated periodic syndromes (CAPS).