Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature

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Disease Profile

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Europe Estimated

Age of onset

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ICD-10

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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.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

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

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.

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]

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.

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 circulating interleukin 8

0033178

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

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]

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]

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

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/

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.

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.

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Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Related diseases

Organizations

Organizations Supporting this Disease

Learn more

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.