CANDLE Syndrome is a rare disorder caused by mutations in the PSMB8 gene, leading to chronic inflammation. Symptoms include persistent fever, skin lesions, lipodystrophy, and joint contractures. Diagnosis is based on clinical presentation and confirmed by genetic testing. Management includes inflammation control, symptom management, physical and developmental support, and family support. Assistive technology is often required, including mobility aids, communication devices, and environmental control systems. Ongoing research aims to develop targeted therapies.
📝 Coding
ICD-11: 4A47.0 - Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature SyndromeOMIM: 256040 - Nakajo-Nishimura Syndrome, which includes CANDLE SyndromeUMLS: C3151247 - Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature SyndromeMeSH: Not availableGARD: 304909 - Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature Syndrome
CANDLE Syndrome
Overview
CANDLE Syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature) is an extremely rare genetic autoinflammatory disorder characterized by recurrent fevers, distinctive skin lesions, progressive lipodystrophy (loss of body fat), and joint contractures. CANDLE syndrome primarily affects infants, with symptoms typically appearing within the first few months of life. The disorder is caused by mutations in genes involved in the proper functioning of proteasomes, leading to chronic inflammation and a range of debilitating symptoms.
Medical Features and Pathophysiology
Pathophysiology
Genetic Basis: CANDLE syndrome is caused by mutations in the PSMB8 gene, and potentially other related genes. These genes are essential for the normal function of proteasomes, which are cellular structures responsible for breaking down and recycling proteins. Mutations in these genes disrupt proteasome function, leading to the accumulation of protein waste products within cells.Inflammatory Response: The buildup of protein waste triggers a chronic inflammatory response, characterized by the overproduction of type I interferons, signaling molecules that play a key role in the immune system. This excessive interferon production drives the persistent inflammation seen in CANDLE syndrome, affecting various tissues and organs, including the skin, joints, and adipose tissue (body fat).Lipodystrophy: The chronic inflammation in CANDLE syndrome specifically targets adipose tissue, leading to progressive lipodystrophy. This loss of body fat is particularly noticeable in the face, arms, legs, and trunk, giving individuals with CANDLE syndrome a characteristic appearance.Systemic Effects: The chronic inflammation also affects other organ systems, leading to a range of symptoms, including recurrent fevers, joint contractures, muscle weakness, and developmental delays.
Symptoms
Early Signs (0-6 Months)
Recurrent Fevers: High fevers, often occurring daily or almost daily, are a hallmark of CANDLE syndrome and typically begin in infancy.Skin Lesions: Distinctive purplish-red, inflamed skin lesions, often appearing around the eyes, cheeks, and nose, are common early signs.Failure to Thrive: Infants with CANDLE syndrome may have difficulty gaining weight and growing at a normal rate.
Later Symptoms (6 Months and Beyond)
Lipodystrophy: Progressive loss of body fat, particularly noticeable in the face, arms, legs, and trunk.Joint Contractures: Stiffening and limited range of motion in the joints, often affecting the hands, elbows, and knees.Muscle Weakness: Generalized muscle weakness and atrophy (muscle wasting).Developmental Delays: Delays in physical development, and possibly cognitive development, are common.Other Symptoms: Enlarged liver (hepatomegaly), swollen eyelids, purple-colored spots on the skin (purpura), headaches, seizures, and anemia.
Diagnosis
Clinical Evaluation: Diagnosis is based on a thorough review of the child's medical history, physical examination, and observation of characteristic features, including recurrent fevers, skin lesions, lipodystrophy, and joint contractures.Genetic Testing: Genetic testing is essential to confirm the diagnosis of CANDLE syndrome. Testing focuses on identifying mutations in the PSMB8 gene, and potentially other related genes involved in proteasome function.Laboratory Tests: Blood tests may reveal elevated levels of inflammatory markers, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Skin biopsies can show characteristic inflammatory changes and an accumulation of neutrophils (a type of white blood cell) in the affected skin.
Management and Treatment
There is no cure for CANDLE syndrome, but treatment focuses on managing inflammation, controlling symptoms, and providing supportive care to improve quality of life.
Medications
Corticosteroids: Corticosteroids, such as prednisone, are powerful anti-inflammatory medications that can help reduce fever, skin lesions, and joint pain. However, long-term use of corticosteroids can have significant side effects, so their use is carefully monitored.Methotrexate: Methotrexate is an immunosuppressant medication that can help reduce inflammation and may be used in combination with corticosteroids.JAK Inhibitors: JAK inhibitors, such as baricitinib, are a newer class of medications that target specific signaling pathways involved in inflammation. They have shown promise in treating CANDLE syndrome and other autoinflammatory disorders.
Therapies
Physical Therapy: Physical therapy is essential to maintain joint range of motion, prevent contractures, and improve muscle strength. Therapists may recommend stretching exercises, assistive devices, and splinting to support mobility and function.Occupational Therapy: Occupational therapy focuses on developing adaptive skills for daily living, such as dressing, feeding, and bathing. Therapists may recommend adaptive equipment, such as specialized utensils or modified clothing, to enhance independence.Speech-Language Therapy: Speech-language therapy can address communication challenges associated with developmental delays or cognitive impairments. Therapists may use a variety of techniques, including sign language, picture exchange systems, or speech-generating devices, to support communication.
Assistive Technology and Communication Devices
Assistive technology plays a crucial role in enhancing communication, learning, and independence for individuals with CANDLE syndrome. Given the severe developmental delays and physical disabilities associated with CANDLE syndrome, a significant percentage, estimated between 80-90%, may require assistive technology.
Speech Generating Devices (SGDs)
SGDs are particularly important for individuals with CANDLE syndrome who have severe speech impairments. These devices range from simple to highly sophisticated:
- Picture exchange communication systems (PECS)
- Communication boards with symbols or photos
- Tablet-based apps (e.g., Proloquo2Go, TouchChat)
- Dedicated SGDs (e.g., Tobii Dynavox devices)
Importance of Symbols for Individuals with CANDLE Syndrome
Symbols are an essential component of AAC systems for individuals with CANDLE syndrome due to several factors:
Cognitive and Linguistic Challenges: Individuals with CANDLE syndrome may have significant cognitive impairments and limited or no verbal language skills. Symbols provide a more concrete and accessible way to represent language concepts compared to abstract text.Visual Processing Strengths: Individuals with CANDLE syndrome may demonstrate relative strengths in visual processing compared to auditory processing. Visual symbols capitalize on these strengths to support communication.Developmental Appropriateness: Symbols, particularly those that closely resemble real objects or actions, align with the developmental level of most individuals with CANDLE syndrome. They provide a more natural starting point for communication development compared to text.
Assessment and Selection of Symbol Sets
A comprehensive AAC assessment is essential to determine the most appropriate symbol set for an individual with CANDLE syndrome. Key considerations include:
Symbolic Understanding: Assess the individual's ability to understand and use various types of symbols, from simple, concrete representations to more abstract concepts.Visual Skills: Consider the individual's visual acuity, visual field, and visual perceptual skills when selecting symbols. Individuals with significant visual impairments may require larger, higher-contrast symbols or even tactile symbols.Motor Skills: Evaluate the individual's ability to accurately select symbols given their motor abilities. Symbols may need to be spaced farther apart or presented in a linear layout to accommodate motor challenges.Customization: Be prepared to customize symbol sets to reflect an individual's specific needs, interests, and environment. Personal photos, for example, can be highly meaningful and motivating.
Access Methods
The choice of access method is critical and depends on the individual's motor abilities, which are often significantly impaired in CANDLE syndrome:
- Touch screens may be challenging for many individuals with CANDLE syndrome due to motor coordination difficulties and joint contractures. However, some may develop sufficient fine motor skills to use touch screens effectively.
- Key guards or enlarged buttons can be helpful for those with less precise movements, which is common in CANDLE syndrome.
- Single-switch scanning is often the most accessible method for individuals with CANDLE syndrome, as it requires only one consistent movement.
- Two-switch step scanning may be possible for some individuals with better motor control, but is less common in CANDLE syndrome.
- This can be an excellent option for individuals with CANDLE syndrome who have severe motor impairments but good visual tracking abilities.
- It requires consistent eye control and the ability to fixate gaze, which may be challenging for some individuals with CANDLE syndrome due to attention deficits or visual processing issues.
- While possible, this method is less commonly used in CANDLE syndrome due to the frequent involuntary movements and motor control issues associated with the syndrome.
Literacy Considerations
While many individuals with CANDLE syndrome may have developmental delays, it is important to support literacy development as much as possible. Pairing symbols with printed words can help build print awareness, even if independent reading is challenging. [[1]](https://poe.com/citation?message_id=216047247627&citation=1) Using visual supports like pictures, schedules, and social stories can also aid comprehension and learning. [[2]](https://poe.com/citation?message_id=216047247627&citation=2) The speech-language pathologist can contribute to reading instruction by adapting materials, providing visual aids, and working with educators to implement appropriate strategies. [[6]](https://poe.com/citation?message_id=216047247627&citation=6)
Customization and Implementation
Personalized Vocabulary Selection: Choose vocabulary that is relevant to the individual's daily life, interests, and communication needs. Consider their current abilities and potential for growth.Consistency Across Environments: Use the same AAC system and vocabulary at home, school, and in the community to promote generalization and consistent communication.Training Communication Partners: Train family members, caregivers, educators, and therapists on how to use the AAC system effectively and support the individual's communication.
Behavioral Considerations
Attention Span: Individuals with CANDLE syndrome may have difficulty sustaining attention, so AAC interventions should be brief, engaging, and incorporate frequent breaks.Sensory Sensitivities: Be mindful of sensory sensitivities and adjust the environment or AAC system as needed to minimize sensory overload.Motivation: Use motivating activities and reinforcers to encourage active participation in AAC interventions.
Considerations for Visual Impairment
Tactile Symbols: For individuals with visual impairments, tactile symbols can be used to represent words or concepts.Auditory Scanning: AAC devices with auditory scanning capabilities allow individuals to hear options and select them using a switch.Enlarged Displays: AAC devices with larger displays or adjustable font sizes can improve visibility for individuals with low vision.
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Care Management and Therapeutic Techniques
Aims
Maximize Potential: Provide opportunities for individuals with CANDLE syndrome to develop their skills and abilities to the fullest extent possible.Manage Challenges: Address the unique challenges associated with CANDLE syndrome, such as chronic inflammation, pain, and developmental delays.Enhance Communication: Facilitate effective communication using AAC devices, sign language, or other alternative methods.Promote Independence: Encourage independence in daily living skills, self-care, and social interactions.
Medical Management
Regular Medical Check-Ups: Monitor overall health, manage inflammation, and address any associated medical conditions.Inflammation Control: Regular monitoring of inflammatory markers, medication adjustments, and exploration of alternative therapies to manage chronic inflammation.Treatment of Associated Medical Conditions: Address any co-occurring medical conditions, such as gastrointestinal issues, orthopedic problems, or visual impairments.
Therapies and Interventions
Physical Therapy: To improve muscle strength, coordination, balance, and mobility. Address joint contractures and muscle weakness.Occupational Therapy: To develop fine motor skills, adaptive skills for daily living, and sensory processing. Focus on positioning and mobility to prevent deformities and enhance comfort.Speech-Language Therapy: To address communication challenges and explore alternative communication methods, such as sign language or AAC devices. Start early intervention and provide family training.Music Therapy: Use music to engage individuals with CANDLE syndrome, promote communication, and reduce anxiety.
Educational Strategies
Individualized Education Programs (IEPs): Develop individualized education programs tailored to the specific needs of students with CANDLE syndrome.Special Education Services: Provide specialized instruction and support services to address learning challenges and promote academic progress.Assistive Technology in Education: Integrate assistive technology into the classroom to support communication, learning, and independence.Visual Supports: Use visual aids, such as pictures, schedules, and social stories, to enhance understanding and communication.
Extended Information
Challenges and Considerations
Caregiver Burden
Caring for an individual with CANDLE syndrome can be physically, emotionally, and financially demanding for caregivers. It is essential to provide support and resources to caregivers to prevent burnout and promote their well-being. [[4]](https://poe.com/citation?message_id=216047247627&citation=4)
Medical Complexity
Managing the multiple health issues associated with CANDLE syndrome can be complex and require a multidisciplinary approach involving various healthcare professionals. [[3]](https://poe.com/citation?message_id=216047247627&citation=3)
Communication Barriers
Speech impairment, if present, presents a significant challenge for individuals with CANDLE syndrome, highlighting the need for early intervention with AAC devices and alternative communication strategies. [[1]](https://poe.com/citation?message_id=216047247627&citation=1)
Behavioral Challenges
Individuals with CANDLE syndrome may exhibit challenging behaviors related to pain, discomfort, or frustration. Addressing these behaviors through positive behavior supports and sensory regulation strategies is important.
Long-Term Care
Individuals with CANDLE syndrome require lifelong support and supervision, and planning for long-term care needs is crucial. [[5]](https://poe.com/citation?message_id=216047247627&citation=5)
Pathological Insights
The dysfunction of proteasomes, caused by mutations in the PSMB8 gene or other related genes, leads to the accumulation of protein waste products within cells. This triggers chronic inflammation, affecting various organs and systems, including the skin, joints, and immune system.
Genetic and Environmental Factors
CANDLE syndrome is a genetic disorder caused by mutations in specific genes. Environmental factors are not known to play a direct role in causing the syndrome, but they may influence the severity of symptoms or the individual's response to treatments.
Clinical Presentation and Disease Progression
The clinical presentation of CANDLE syndrome can vary, but most individuals experience a similar pattern of symptoms, including early-onset fever, distinctive skin lesions, lipodystrophy, and joint contractures. Disease progression is typically slow but relentless, leading to increasing disability over time.
Differential Diagnosis
Other conditions that may present with similar symptoms to CANDLE syndrome include:
Other autoinflammatory disorders, such as NOMID/CINCA syndrome or TNF receptor-associated periodic syndrome (TRAPS) Infectious diseases Malignancies
A thorough medical evaluation, including genetic testing, is essential for an accurate diagnosis and appropriate management.
Support and Resources
This information is intended for educational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional for diagnosis, treatment, and management of CANDLE syndrome or any other medical condition.
References
UPMC Children's Hospital of Pittsburgh. (n.d.). Detailed overview of symptoms, diagnosis, and treatment options for CANDLE Syndrome. Retrieved from UPMC Children's Hospital
National Organization for Rare Disorders (NORD). (n.d.). Provides information on the symptoms, causes, and research related to CANDLE Syndrome. Retrieved from NORD CANDLE Syndrome
Genetic and Rare Diseases Information Center (GARD). (n.d.). Offers insights into the clinical features and management of CANDLE Syndrome. Retrieved from GARD CANDLE Syndrome
Autoinflammatory Alliance. (n.d.). Detailed description of the genetic basis and symptoms of CANDLE Syndrome. Retrieved from Autoinflammatory Alliance
Altmeyers Encyclopedia. (n.d.). Provides information on the genetic inheritance and clinical presentation of CANDLE Syndrome. Retrieved from Altmeyers Encyclopedia
Caves, K., DeRuyter, F., & Beukelman, D. R. (2002). Interface Design. Perspectives on Augmentative and Alternative Communication, 11(2), 8–11. https://doi.org/10.1044/aac11.2.8
Wilkinson, K. M., Light, J., & Drager, K. (2012). Considerations for the composition of visual scene displays: Potential contributions of information from visual and cognitive sciences. Augmentative and Alternative Communication, 28(3), 137-147. https://doi.org/10.3109/07434618.2012.704522
Vihriӓlӓ, T. A., Ihalainen, T., Elo, C., Lintula, L., & others. (2024). Possibilities of intelligent textiles in AAC–perspectives of speech and language therapists. Disability and Rehabilitation: Assistive Technology. https://doi.org/10.1080/17483107.2022.2141900
Berg, J., & Drossos, K. (2021). Continual Learning for Automated Audio Captioning Using The Learning Without Forgetting Approach. arXiv preprint arXiv:2107.08028. http://arxiv.org/abs/2107.08028
Cavalcante, M. P. V., Brunelli, J. B., Miranda, C. C., Novak, G. V., Malle, L., Aikawa, N. E., Jesus, A. A., & Silva, C. A. (2016). CANDLE syndrome: chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature—a rare case with a novel mutation. European Journal of Pediatrics, 175(5), 735–740. https://doi.org/10.1007/s00431-015-2668-4
