Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature

Title

Other Names:

CANDLE syndrome; Chronic atypical neutrophilic dermatosis-lipodystrophy-elevated temperature syndrome

Categories:

Congenital and Genetic Diseases; Immune System Diseases; Musculoskeletal Diseases; Congenital and Genetic Diseases; Immune System Diseases; Musculoskeletal Diseases; Skin Diseases See More

Summary Summary

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE syndrome) occurs when the immune system attacks the body by mistake. Symptoms usually develop within the first few months of life and may include recurrent fevers and purple colored spots on the skin particularly around the eyes. Loss of body fat, bone, and joint pain also usually occur. Since so few people have been reported with CANDLE syndrome, it is difficult to know how it affects people in the long term. CANDLE syndrome occurs when the PSMB8 gene is not working correctly. Other genes associated with CANDLE syndrome include PSMB4, PSMA3, and POMP. It is usually inherited in an autosomal recessive pattern; however, when associated with variants in the POMP gene, may be inherited in an autosomal dominant pattern. There is no specific treatment for this condition; however, steroids may help reduce the frequency of symptoms.

Last updated: 6/11/2020

Symptoms Symptoms

The following list includes the most common signs and symptoms in people with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms of CANDLE syndrome may include:^[1]^[2]

Recurrent fever
Muscle wasting
Short stature
Failure to thrive
Loss of body fat (lipodystrophy)
Enlarged liver (hepatomegaly)
Bone pain
Low blood iron (anemia)

The symptoms of CANDLE syndrome usually appear within the first months of life. Initial symptoms include recurrent fevers and skin lesions. Loss of body fat (lipodystrophy) typically begins in early childhood. Bone and joint pain may also occur over time. Very few people have been diagnosed with CANDLE syndrome, so it is not well understood how it changes over time.^[1]

Last updated: 6/11/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
1%-4% of people have these symptoms
Acanthosis nigricans	Darkened and thickened skin	0000956
Arrhythmia	Abnormal heart rate Heart rhythm disorders Irregular heart beat Irregular heartbeat [ more ]	0011675
Arthralgia	Joint pain	0002829
Basal ganglia calcification		0002135
Bone pain		0002653
Childhood onset	Symptoms begin in childhood	0011463
Chronic constipation	Infrequent bowel movements	0012450
Conjunctivitis	Pink eye	0000509
Death in adolescence		0011421
Decreased HDL cholesterol concentration	Decreased circulating high-density lipoprotein cholesterol Decreased HDL cholesterol Low HDL-cholesterol [ more ]	0003233
Elevated C-reactive protein level		0011227
Elevated erythrocyte sedimentation rate	High ESR	0003565
Elevated hepatic transaminase	High liver enzymes	0002910
Epididymitis		0000031
Episcleritis	Inflammation of the thin layer on top of the white part of eye	0100534
Erythema nodosum		0012219
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Finger swelling		0025131
Flexion contracture of finger		0012785
Gynecomastia	Enlarged male breast	0000771
Hallux valgus	Bunion	0001822
Hepatomegaly	Enlarged liver	0002240
Hypertrichosis		0000998
Hypertriglyceridemia	Increased plasma triglycerides Increased serum triglycerides Increased triglycerides [ more ]	0002155
Hypoplastic scapulae	Small shoulder blade	0000882
Increased circulating IgA level		0003261
Increased circulating IgG level		0003237
Increased circulating interleukin 6		0030783
Increased serum interferon-gamma level		0030356
Increased thyroid-stimulating hormone level		0002925
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Irregular menstruation	Menstrual irregularity	0000858
Lipodystrophy	Inability to make and keep healthy fat tissue	0009125
Lymphadenopathy	Swollen lymph nodes	0002716
Macroglossia	Abnormally large tongue Increased size of tongue Large tongue [ more ]	0000158
Microcytic anemia		0001935
Parotitis		0011850
Premature graying of hair	Early graying Premature graying Premature greying Premature hair graying [ more ]	0002216
Progeroid facial appearance	Premature aged appearance	0005328
Proptosis	Bulging eye Eyeballs bulging out Prominent eyes Prominent globes Protruding eyes [ more ]	0000520
Protuberant abdomen	Belly sticks out Extended belly [ more ]	0001538
Punctate opacification of the cornea		0007856
Recurrent fever	Episodic fever Increased body temperature, episodic Intermittent fever [ more ]	0001954
Recurrent otitis media	Recurrent middle ear infection	0000403
Recurrent sinusitis		0011108
Reduced tendon reflexes		0001315
Seizure		0001250
Short stature	Decreased body height Small stature [ more ]	0004322
Skeletal muscle atrophy	Muscle degeneration Muscle wasting [ more ]	0003202
Skin plaque		0200035
Sparse axillary hair	Limited armpit hair Little underarm hair [ more ]	0002215
Splenomegaly	Increased spleen size	0001744
Thrombocytopenia	Low platelet count	0001873
Percent of people who have these symptoms is not available through HPO
Adipose tissue loss	Loss of fat tissue	0008887
Autosomal recessive inheritance		0000007
Camptodactyly of finger	Permanent flexion of the finger	0100490
Cardiomegaly	Enlarged heart Increased heart size [ more ]	0001640
Clubbing of fingers	Clubbed fingers Clubbing (hands) Finger clubbing [ more ]	0100759
Congestive heart failure	Cardiac failure Cardiac failures Heart failure [ more ]	0001635
Elbow flexion contracture	Contractures of elbows Elbow contracture Elbow contractures [ more ]	0002987
Erythema		0010783
Flexion contracture of toe		0005830
Growth abnormality	Abnormal growth Growth issue [ more ]	0001507
Hyperpigmentation of the skin	Patchy darkened skin	0000953
Impaired glucose tolerance		0040270
Long fingers		0100807
Loss of facial adipose tissue	Decreased amount of facial fat Loss of facial fat [ more ]	0000292
Macrotia	Large ears	0000400
Muscle weakness	Muscular weakness	0001324
Panniculitis	Inflammation of fat tissue	0012490
Prominent nose	Big nose Disproportionately large nose Increased nasal size Increased size of nose Large nose Pronounced nose [ more ]	0000448
Stiff skin		0030053
Thick lower lip vermilion	Increased volume of lower lip Plump lower lip Prominent lower lip [ more ]	0000179

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Last updated: 11/1/2020

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Cause Cause

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome occurs when the PSMB8, PSMB4, PSMA3, or POMP gene is not working correctly. DNA changes known as pathogenic variants or mutations are responsible for making genes work incorrectly or sometimes, not at all.^[1]^[2]

Last updated: 6/11/2020

Inheritance Inheritance

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome usually inherited in an autosomal recessive pattern.^[1]^[2] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be altered to have the condition.

People with autosomal recessive conditions inherit one alteration from each of their parents. The parents, who each have one gene alteration, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

When CANDLE syndrome is associated with the POMP gene, it can be inherited in an autosomal dominant pattern.

Last updated: 6/11/2020

Diagnosis Diagnosis

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is diagnosed through a clinical exam, the symptoms, and can be confirmed by genetic testing.^[3]^[4]

Last updated: 6/11/2020

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other proteasome disability syndromes as well as CINCA syndrome, panniculitis-induced acquired generalized lipodystrophy, Sweet syndrome (see these terms), and other annular eruptions of infancy and skin involvement as seen in acute myeloid leukemia (see this term). Visit the Orphanet disease page for more information.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

FMF & AID Global Association
Schüracherstrasse 25a
8306 Brüttisellen
Switzerland
Telephone: +41 76 415 4010
E-mail: info@fmfandaid.org
Website: https://www.fmfandaid.org/

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature. Click on the link to view a sample search on this topic.

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References References

Torrelo A. CANDLE Syndrome As a Paradigm of Proteasome-Related Autoinflammation. Front Immunol. 2017; 8:927. https://pubmed.ncbi.nlm.nih.gov/28848544.
Boyadzhiev M, Marinov L, Boyadzhiev V, Iotova V, Aksentijevich I, Hambleton S. Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome. Pediatr Rheumatol Online J. 2019; 17(1):19. https://pubmed.ncbi.nlm.nih.gov/31046790.
Torrelo A, Patel S, Colmenero I, et al. Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. J Am Acad Dermatol. 2010; 62(3):489-495. https://pubmed.ncbi.nlm.nih.gov/20159315.
Liu Y, Ramot Y, Torrelo A, et al. Mutations in proteasome subunit ß type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity. Arthritis Rheum. 2012; 64(3):895-907. https://pubmed.ncbi.nlm.nih.gov/21953331.