CANDLE syndrome: Difference between revisions

Revision as of 06:38, 16 February 2025

A rare autoinflammatory genetic disorder

CANDLE syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature) is a rare autoinflammatory disease characterized by recurrent fevers, skin rashes, and joint pain. It is caused by mutations in the PSMB8 gene and is inherited in an autosomal recessive manner.

Genetics

CANDLE syndrome is associated with mutations in the PSMB8 gene, which encodes a component of the immunoproteasome. This gene is located on chromosome 6. The syndrome follows an autosomal recessive pattern of inheritance, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent.

Clinical Features

Patients with CANDLE syndrome typically present in infancy or early childhood. The main clinical features include:

Recurrent fevers
Skin rashes, often with a neutrophilic dermatosis appearance
Lipodystrophy, which is the abnormal distribution of body fat
Joint pain and swelling
Muscle weakness

Pathophysiology

The PSMB8 gene mutations lead to a dysfunctional immunoproteasome, which is crucial for the degradation of proteins and the regulation of the immune response. The impaired function results in the accumulation of protein aggregates and an inappropriate inflammatory response, contributing to the symptoms of CANDLE syndrome.

Diagnosis

Diagnosis of CANDLE syndrome is based on clinical presentation, family history, and genetic testing to identify mutations in the PSMB8 gene. Laboratory tests may show elevated inflammatory markers and abnormal immune cell function.

Treatment

There is no cure for CANDLE syndrome, and treatment is primarily supportive. Management strategies include:

Anti-inflammatory medications, such as corticosteroids
Immunosuppressive agents
Biologic therapies targeting specific inflammatory pathways

Prognosis

The prognosis for individuals with CANDLE syndrome varies. Early diagnosis and management can improve quality of life, but the condition can be chronic and debilitating.

Related pages

@@ Line 1: / Line 1: @@
-''CANDLE syndrome''', also known as '''Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature syndrome''', is a rare autoinflammatory disorder characterized by early-onset fevers, skin lesions, and a distinctive set of associated features including lipodystrophy, joint pain, and specific blood abnormalities. This condition falls under the broader category of autoinflammatory diseases, which involve an abnormal activation of the innate immune system without the high levels of antibodies or autoantibodies that are characteristic of autoimmune diseases.
+{{Short description|A rare autoinflammatory genetic disorder}}
+{{Medical genetics}}
-==Symptoms and Signs==
+'''CANDLE syndrome''' (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature) is a rare [[autoinflammatory disease]] characterized by recurrent fevers, skin rashes, and joint pain. It is caused by mutations in the [[PSMB8]] gene and is inherited in an [[autosomal recessive]] manner.
-CANDLE syndrome presents with a wide range of symptoms, the most common being:
-* Persistent fevers that are often of early onset
+==Genetics==
-* Characteristic skin rashes, including purplish, painful, lumpy skin lesions
+[[File:Autosomal_recessive_-_en.svg|thumb|right|Diagram of autosomal recessive inheritance.]]
-* Lipodystrophy, particularly a loss of fat beneath the skin
+CANDLE syndrome is associated with mutations in the [[PSMB8]] gene, which encodes a component of the immunoproteasome. This gene is located on chromosome 6. The syndrome follows an [[autosomal recessive]] pattern of inheritance, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent.
-* Joint pain and contractures
+==Clinical Features==
+Patients with CANDLE syndrome typically present in infancy or early childhood. The main clinical features include:
+* Recurrent fevers
+* Skin rashes, often with a neutrophilic dermatosis appearance
+* Lipodystrophy, which is the abnormal distribution of body fat
+* Joint pain and swelling
 * Muscle weakness
-* Delayed physical development in children
-* Organomegaly, including hepatomegaly (enlarged liver) and splenomegaly (enlarged spleen)
-* Blood abnormalities, such as anemia and elevated levels of inflammatory markers
-==Causes==
+==Pathophysiology==
-CANDLE syndrome is caused by mutations in several genes involved in the regulation of the immune system. These genetic mutations lead to the overproduction of certain proteins that play a role in inflammation, causing the symptoms of the syndrome. The condition is inherited in an autosomal recessive pattern, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.
+The [[PSMB8]] gene mutations lead to a dysfunctional immunoproteasome, which is crucial for the degradation of proteins and the regulation of the immune response. The impaired function results in the accumulation of protein aggregates and an inappropriate inflammatory response, contributing to the symptoms of CANDLE syndrome.
 ==Diagnosis==
-Diagnosis of CANDLE syndrome is based on the clinical presentation of symptoms, laboratory findings, and genetic testing. Key diagnostic tests include:
+Diagnosis of CANDLE syndrome is based on clinical presentation, family history, and genetic testing to identify mutations in the [[PSMB8]] gene. Laboratory tests may show elevated inflammatory markers and abnormal immune cell function.
-* Blood tests to check for elevated inflammatory markers
-* Genetic testing to identify mutations in the relevant genes
-* Skin biopsy of affected areas to examine under a microscope
 ==Treatment==
-There is no cure for CANDLE syndrome, but treatments are available to manage symptoms and improve quality of life. Treatment options include:
+There is no cure for CANDLE syndrome, and treatment is primarily supportive. Management strategies include:
-* Corticosteroids and other anti-inflammatory medications to reduce inflammation
+* Anti-inflammatory medications, such as corticosteroids
-* Immunomodulatory therapies, such as Janus kinase (JAK) inhibitors
+* Immunosuppressive agents
-* Supportive care for symptoms such as pain management and physical therapy
+* Biologic therapies targeting specific inflammatory pathways
 ==Prognosis==
-The prognosis for individuals with CANDLE syndrome varies. With early diagnosis and appropriate treatment, many of the symptoms can be managed effectively, allowing individuals to lead active lives. However, the disease can be severe and life-threatening in some cases.
+The prognosis for individuals with CANDLE syndrome varies. Early diagnosis and management can improve quality of life, but the condition can be chronic and debilitating.
-==Research==
+==Related pages==
-Research into CANDLE syndrome is ongoing, with studies focusing on understanding the genetic causes of the disease and developing more effective treatments. Clinical trials of new therapies, including targeted biologic agents, are underway.
+* [[Autoinflammatory disease]]
+* [[Lipodystrophy]]
+* [[Neutrophilic dermatosis]]
+[[Category:Genetic disorders]]
 [[Category:Autoinflammatory syndromes]]
-[[Category:Rare diseases]]
-[[Category:Genetic disorders]]
-[[Category:Syndromes]]
-{{Medicine-stub}}
-{{Syndromes-stub}}
-{{No image}}