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Skin rash

MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
Synonyms: Rash; Skin rashes
 
HPO: HP:0000988

Definition

A red eruption of the skin. [from HPO]

Conditions with this feature

Biotinidase deficiency
MedGen UID:
66323
Concept ID:
C0220754
Disease or Syndrome
If untreated, young children with profound biotinidase deficiency usually exhibit neurologic abnormalities including seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities (e.g., alopecia, skin rash, candidiasis). Older children and adolescents with profound biotinidase deficiency often exhibit motor limb weakness, spastic paresis, and decreased visual acuity. Once vision problems, hearing loss, and developmental delay occur, they are usually irreversible, even with biotin therapy. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress.
Familial visceral amyloidosis, Ostertag type
MedGen UID:
82799
Concept ID:
C0268389
Disease or Syndrome
A group of rare renal diseases, characterized by amyloid fibril deposition of apolipoprotein A-I or A-II (AApoAI or AApoAII amyloidosis), lysozyme (ALys amyloidosis) or fibrinogen A-alpha chain (AFib amyloidosis) in one or several organs. Renal involvement leading to chronic renal disease and renal failure is a common sign. Additional manifestations depend on the organ involved and the type of amyloid fibrils deposited.
Holocarboxylase synthetase deficiency
MedGen UID:
120653
Concept ID:
C0268581
Disease or Syndrome
Holocarboxylase synthetase deficiency, a biotin-responsive multiple carboxylase deficiency (MCD), is characterized by metabolic acidosis, lethargy, hypotonia, convulsions, and dermatitis. Most patients present in the newborn or early infantile period, but some become symptomatic in the later infantile period (summary by Suzuki et al., 2005). Also see biotinidase deficiency (253260), another form of MCD with a later onset. Care must be taken to differentiate the inherited multiple carboxylase deficiencies from acquired biotin deficiencies, such as those that develop after excessive dietary intake of avidin, an egg-white glycoprotein that binds specifically and essentially irreversibly to biotin (Sweetman et al., 1981) or prolonged parenteral alimentation without supplemental biotin (Mock et al., 1981).
Hyperimmunoglobulin D with periodic fever
MedGen UID:
140768
Concept ID:
C0398691
Disease or Syndrome
Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often.\n\nMevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA).\n\nDuring episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why some people with HIDS have high levels of IgD and IgA and some do not. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy.\n\nPeople with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, problems with movement and balance (ataxia), recurrent seizures (epilepsy), progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy.
Chronic infantile neurological, cutaneous and articular syndrome
MedGen UID:
98370
Concept ID:
C0409818
Disease or Syndrome
Chronic infantile neurologic cutaneous and articular syndrome (CINCA) is an early-onset, severe, chronic inflammatory disease, characterized by cutaneous symptoms, central nervous system involvement, and arthropathy (Feldmann et al., 2002). See also familial cold autoinflammatory syndrome-1 (FCAS1, CAPS1; 120100), an allelic disorder with a less severe phenotype.
TNF receptor-associated periodic fever syndrome (TRAPS)
MedGen UID:
226899
Concept ID:
C1275126
Disease or Syndrome
Familial periodic fever (FPF) is an autoinflammatory disorder characterized by recurrent fever with localized myalgia and painful erythema. Febrile attacks may last 1 or 2 days but often last longer than 1 week. Arthralgia of large joints, abdominal pain, conjunctivitis, and periorbital edema are common features. During attacks, painless cutaneous lesions may develop on the trunk or extremities and may migrate distally (review by Drenth and van der Meer, 2001).
X-linked severe combined immunodeficiency
MedGen UID:
220906
Concept ID:
C1279481
Disease or Syndrome
The phenotypic spectrum of X-linked severe combined immunodeficiency (X-SCID) ranges from typical X-SCID (early-onset disease in males that is fatal if not treated with hematopoietic stem cell transplantation [HSCT] or gene therapy) to atypical X-SCID (later-onset disease comprising phenotypes caused by variable immunodeficiency, immune dysregulation, and/or autoimmunity). Typical X-SCID. Prior to universal newborn screening (NBS) for SCID most males with typical X-SCID came to medical attention between ages three and six months because of recurrent infections, persistent infections, and infections with opportunistic organisms. With universal NBS for SCID, the common presentation for typical X-SCID is now an asymptomatic, healthy-appearing male infant. Atypical X-SCID, which usually is not detected by NBS, can manifest in the first years of life or later with one of the following: recurrent upper and lower respiratory tract infections with bronchiectasis; Omenn syndrome, a clinical phenotype caused by immune dysregulation; X-SCID combined immunodeficiency (often with recurrent infections, warts, and dermatitis); immune dysregulation and autoimmunity; or Epstein-Barr virus-related lymphoproliferative complications.
Methylmalonic aciduria and homocystinuria type cblF
MedGen UID:
336373
Concept ID:
C1848578
Disease or Syndrome
Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range: In utero with fetal presentation of nonimmune hydrops, cardiomyopathy, and intrauterine growth restriction. Newborns, who can have microcephaly, poor feeding, and encephalopathy. Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS). Toddlers, who can have poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures. Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, thromboembolic complications, and/or subacute combined degeneration of the spinal cord.
Pellagra-like syndrome
MedGen UID:
337955
Concept ID:
C1850052
Disease or Syndrome
Deafness, sensorineural, with peripheral neuropathy and arterial disease
MedGen UID:
343766
Concept ID:
C1852280
Disease or Syndrome
Poikiloderma with neutropenia
MedGen UID:
388129
Concept ID:
C1858723
Disease or Syndrome
Poikiloderma with neutropenia (PN) is characterized by an inflammatory eczematous rash (ages 6-12 months) followed by post-inflammatory poikiloderma (age >2 years) and chronic noncyclic neutropenia typically associated with recurrent sinopulmonary infections in the first two years of life and (often) bronchiectasis. There is increased risk for myelodysplastic syndrome and, rarely, acute myelogenous leukemia. Other ectodermal findings include nail dystrophy and palmar/plantar hyperkeratosis. Most affected individuals also have reactive airway disease and some have short stature, hypogonadotropic hypogonadism, midfacial retrusion, calcinosis cutis, and non-healing skin ulcers.
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency
MedGen UID:
354935
Concept ID:
C1863236
Disease or Syndrome
Adenosine deaminase (ADA) deficiency is a systemic purine metabolic disorder that primarily affects lymphocyte development, viability, and function. The clinical phenotypic spectrum includes: Severe combined immunodeficiency disease (SCID), often diagnosed by age six months and usually by age 12 months; Less severe "delayed" onset combined immune deficiency (CID), usually diagnosed between age one and ten years; "Late/adult onset" CID, diagnosed in the second to fourth decades; Benign "partial ADA deficiency" (very low or absent ADA activity in erythrocytes but greater ADA activity in nucleated cells), which is compatible with normal immune function. Infants with typical early-onset ADA-deficient SCID have failure to thrive and opportunistic infections associated with marked depletion of T, B, and NK lymphocytes, and an absence of both humoral and cellular immune function. If immune function is not restored, children with ADA-deficient SCID rarely survive beyond age one to two years. Infections in delayed- and late-onset types (commonly, recurrent otitis, sinusitis, and upper respiratory) may initially be less severe than those in individuals with ADA-deficient SCID; however, by the time of diagnosis these individuals often have chronic pulmonary insufficiency and may have autoimmune phenomena (cytopenias, anti-thyroid antibodies), allergies, and elevated serum concentration of IgE. The longer the disorder goes unrecognized, the more immune function deteriorates and the more likely are chronic sequelae of recurrent infection.
Familial hemophagocytic lymphohistiocytosis 2
MedGen UID:
400366
Concept ID:
C1863727
Disease or Syndrome
Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG; 147570) and TNF-alpha (191160), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (summary by Dufourcq-Lagelouse et al., 1999, Stepp et al., 1999, and Molleran Lee et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of FHL, see 267700.
Familial hemophagocytic lymphohistiocytosis 4
MedGen UID:
350245
Concept ID:
C1863728
Disease or Syndrome
Hemophagocytic lymphohistiocytosis is a hyperinflammatory disorder clinically diagnosed based on the fulfillment of 5 of 8 criteria, including fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low or absent natural killer (NK) cell activity, hyperferritinemia, and high soluble IL2 receptor levels (IL2R; 147730). The disorder typically presents in infancy or early childhood. Persistent remission is rarely achieved with chemo- or immunotherapy; hematopoietic stem cell transplantation is the only cure (summary by Muller et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL), see 267700.
Majeed syndrome
MedGen UID:
351273
Concept ID:
C1864997
Disease or Syndrome
Majeed syndrome (MJDS) is an autosomal recessive pediatric multisystem autoinflammatory disorder characterized by chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anemia; some patients may also develop neutrophilic dermatosis. Additional features may include fever, failure to thrive, and neutropenia. Laboratory studies show elevated inflammatory markers consistent with activation of the proinflammatory IL1 (147760) pathway (summary by Ferguson and El-Shanti, 2021). Genetic Heterogeneity of Chronic Recurrent Multifocal Osteomyelitis See also CRMO2 (612852), caused by mutation in the IL1RN gene (147679) on chromosome 2q14; and CRMO3 (259680), caused by mutation in the IL1R1 gene (147810) on chromosome 2q12.
Hyperzincemia with functional zinc depletion
MedGen UID:
356415
Concept ID:
C1865986
Disease or Syndrome
Mevalonic aciduria
MedGen UID:
368373
Concept ID:
C1959626
Disease or Syndrome
Mevalonic aciduria (MEVA), the first recognized defect in the biosynthesis of cholesterol and isoprenoids, is a consequence of a deficiency of mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36). Mevalonic acid accumulates because of failure of conversion to 5-phosphomevalonic acid, which is catalyzed by mevalonate kinase. Mevalonic acid is synthesized from 3-hydroxy-3-methylglutaryl-CoA, a reaction catalyzed by HMG-CoA reductase (142910). Mevalonic aciduria is characterized by dysmorphology, psychomotor retardation, progressive cerebellar ataxia, and recurrent febrile crises, usually manifesting in early infancy, accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. The febrile crises are similar to those observed in hyperimmunoglobulinemia D and to periodic fever syndrome (HIDS; 260920), which is also caused by mutation in the MVK gene (summary by Prietsch et al., 2003).
Familial cold autoinflammatory syndrome 2
MedGen UID:
435869
Concept ID:
C2673198
Disease or Syndrome
Familial cold autoinflammatory syndrome-2 (FCAS2) is an autosomal dominant autoinflammatory disorder characterized by episodic and recurrent rash, urticaria, arthralgia, myalgia, and headache. In most patients, these episodes are accompanied by fever and serologic evidence of inflammation. Most, but not all, patients report exposure to cold as a trigger for the episodes. Additional features may include abdominal pain, thoracic pain, and sensorineural deafness. The age at onset is variable, ranging from the first year of life to middle age, and the severity and clinical manifestations are heterogeneous (summary by Shen et al., 2017). For a phenotypic description and a discussion of genetic heterogeneity of familial cold autoinflammatory syndrome, see FCAS1 (120100).
Pancreatic insufficiency-anemia-hyperostosis syndrome
MedGen UID:
436369
Concept ID:
C2675184
Disease or Syndrome
This syndrome is characterized by exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis. It has been described in four children, three boys and one girl, from two consanguineous families. The disease is due to a mutation in the COX4I2 gene, encoding a mitochondrial cytochrome C oxidase sub-unit. Transmission is autosomal recessive.
Sterile multifocal osteomyelitis with periostitis and pustulosis
MedGen UID:
411230
Concept ID:
C2748507
Disease or Syndrome
Chronic recurrent multifocal osteomyelitis-2 with periostitis and pustulosis (CRMO2) is an autosomal recessive multisystemic autoinflammatory disorder characterized by onset of symptoms in early infancy. Affected individuals present with joint swelling and pain, pustular rash, oral mucosal lesions, and fetal distress. The disorder progresses in severity to generalized severe pustulosis or ichthyosiform lesions and diffuse bone lesions. Radiographic studies show widening of the anterior rib ends, periosteal elevation along multiple long bones, multifocal osteolytic lesions, heterotopic ossification, and metaphyseal erosions of the long bones. Laboratory studies show elevation of inflammatory markers. The disorder results from unopposed activation of the IL1 inflammatory signaling pathway. Treatment with the interleukin-1 receptor antagonist anakinra may result in clinical improvement (Aksentijevich et al., 2009). For a discussion of genetic heterogeneity of CRMO, see 609628.
Juvenile idiopathic arthritis
MedGen UID:
760659
Concept ID:
C3495559
Disease or Syndrome
A rare, heterogeneous group of rheumatologic diseases characterized by arthritis which has an onset before 16 years of age, persists for more than 6 weeks, and is of unknown origin.
Combined immunodeficiency due to MALT1 deficiency
MedGen UID:
815913
Concept ID:
C3809583
Disease or Syndrome
Combined immunodeficiency due to MALT1 deficiency is a rare, genetic form of primary immunodeficiency characterized by growth retardation, early recurrent pulmonary infections leading to bronchiectasis, inflammatory gastrointestinal disease, and other symptoms, such as rash, dermatitis, skin infections.
Vasculitis due to ADA2 deficiency
MedGen UID:
854497
Concept ID:
C3887654
Disease or Syndrome
Adenosine deaminase 2 deficiency (DADA2) is a complex systemic autoinflammatory disorder in which vasculopathy/vasculitis, dysregulated immune function, and/or hematologic abnormalities may predominate. Inflammatory features include intermittent fevers, rash (often livedo racemosa/reticularis), and musculoskeletal involvement (myalgia/arthralgia, arthritis, myositis). Vasculitis, which usually begins before age ten years, may manifest as early-onset ischemic (lacunar) and/or hemorrhagic strokes, or as cutaneous or systemic polyarteritis nodosa. Hypertension and hepatosplenomegaly are often found. More severe involvement may lead to progressive central neurologic deficits (dysarthria, ataxia, cranial nerve palsies, cognitive impairment) or to ischemic injury to the kidney, intestine, and/or digits. Dysregulation of immune function can lead to immunodeficiency or autoimmunity of varying severity; lymphadenopathy may be present and some affected individuals have had lymphoproliferative disease. Hematologic disorders may begin early in life or in late adulthood, and can include lymphopenia, neutropenia, pure red cell aplasia, thrombocytopenia, or pancytopenia. Of note, both interfamilial and intrafamilial phenotypic variability (e.g., in age of onset, frequency and severity of manifestations) can be observed; also, individuals with biallelic ADA2 pathogenic variants may remain asymptomatic until adulthood or may never develop clinical manifestations of DADA2.
Aicardi-Goutieres syndrome 7
MedGen UID:
854829
Concept ID:
C3888244
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.
STING-associated vasculopathy with onset in infancy
MedGen UID:
863159
Concept ID:
C4014722
Disease or Syndrome
STING-associated vasculopathy with onset in infancy is an autoinflammatory vasculopathy causing severe skin lesions, particularly affecting the face, ears, nose, and digits, and resulting in ulceration, eschar formation, necrosis, and, in some cases, amputation. Many patients have interstitial lung disease. Tissue biopsy and laboratory findings show a hyperinflammatory state, with evidence of increased beta-interferon (IFNB1; 147640) signaling (summary by Liu et al., 2014).
Periodic fever-infantile enterocolitis-autoinflammatory syndrome
MedGen UID:
863504
Concept ID:
C4015067
Disease or Syndrome
Autoinflammation with infantile enterocolitis is an autosomal dominant disorder characterized by onset of recurrent flares of autoinflammation in early infancy. Affected individuals tend to have poor overall growth and gastrointestinal symptoms in infancy associated with laboratory evidence of activated inflammation. This initial presentation is followed by recurrent febrile episodes with splenomegaly and sometimes hematologic disturbances, arthralgias, or myalgias. The disorder results from overactivation of an arm of the immune response system (Romberg et al., 2014; Canna et al., 2014).
Autoinflammatory syndrome, familial, Behcet-like 1
MedGen UID:
898541
Concept ID:
C4225218
Disease or Syndrome
Familial Behcet-like autoinflammatory syndrome-1 (AIFBL1) is an autosomal dominant monogenic autoinflammatory disease characterized predominantly by painful and recurrent mucosal ulceration affecting the oral mucosa, gastrointestinal tract, and genital areas. The onset of symptoms is usually in the first decade, although later onset has been reported. Additional more variable features include skin rash, uveitis, and polyarthritis, consistent with a systemic hyperinflammatory state. Many patients have evidence of autoimmune disease. Rare patients may also have concurrent features of immunodeficiency, including recurrent infections with low numbers of certain white blood cells or impaired function of immune cells. The disorder results from a failure of mutant TNFAIP3 to suppress the activation of inflammatory cytokines in the NFKB (see 164011) signaling pathway; treatment with tumor necrosis factor (TNFA; 191160) inhibitors may be beneficial. Although some of the clinical features of AIFBL1 resemble those of Behcet disease (109650), the more common form of Behcet disease is believed to be polygenic, typically shows later onset in early adulthood, and has symptoms usually restricted to the mucosa (summary by Zhou et al., 2016; Aeschlimann et al., 2018, and Kadowaki et al., 2018). Genetic Heterogeneity of AIFBL See also AIFBL2 (301074), caused by mutation in the ELF4 gene (300775) on chromosome Xq26, and AIFBL3 (618287), caused by mutation in the RELA gene (164014) on chromosome 11q13.
Infantile-onset periodic fever-panniculitis-dermatosis syndrome
MedGen UID:
934581
Concept ID:
C4310614
Disease or Syndrome
Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) is an autosomal recessive autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein (CRP), leukocytosis, and neutrophilia in the absence of any infection. Patients exhibit no overt primary immunodeficiency (Damgaard et al., 2016 and Zhou et al., 2016).
Yao syndrome
MedGen UID:
934587
Concept ID:
C4310620
Disease or Syndrome
Yao syndrome (YAOS) is an autoinflammatory disease characterized by periodic fever, dermatitis, arthritis, and swelling of the distal extremities, as well as gastrointestinal and sicca-like symptoms. The disorder is associated with specific NOD2 variants (and Shen, 2017).
Neurodevelopmental disorder with midbrain and hindbrain malformations
MedGen UID:
1385580
Concept ID:
C4479613
Disease or Syndrome
Neurodevelopmental disorder with midbrain and hindbrain malformations (NEDMHM) is an autosomal recessive disorder comprising impaired intellectual development, speech delay, mild microcephaly, and midbrain-hindbrain malformation (Ravindran et al., 2017).
Immunodeficiency 53
MedGen UID:
1612104
Concept ID:
C4539811
Disease or Syndrome
Intellectual disability, autosomal dominant 45
MedGen UID:
1616472
Concept ID:
C4539848
Mental or Behavioral Dysfunction
Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease
MedGen UID:
1618052
Concept ID:
C4540232
Disease or Syndrome
Immunodeficiency-71 with inflammatory disease and congenital thrombocytopenia (IMD71) is an autosomal recessive immunologic disorder characterized by the onset of recurrent infections and inflammatory features such as vasculitis and eczema in infancy or early childhood. Infectious agents include bacteria and viruses. Laboratory findings are variable, but usually show thrombocytopenia, sometimes with abnormal platelet morphology, increased serum IgE, IgA, or IgM, leukocytosis, decreased or increased T lymphocytes, and increased eosinophils. Detailed studies show impaired neutrophil and T-cell chemotaxis, as well as impaired T-cell activation due to defects in F-actin (see 102610) polymerization (summary by Brigida et al., 2018).
Familial cold autoinflammatory syndrome 1
MedGen UID:
1647324
Concept ID:
C4551895
Disease or Syndrome
Cryopyrin-associated periodic syndromes (CAPS) are a group of conditions that have overlapping signs and symptoms and the same genetic cause. The group includes three conditions known as familial cold autoinflammatory syndrome type 1 (FCAS1), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disorder (NOMID). These conditions were once thought to be distinct disorders but are now considered to be part of the same condition spectrum. FCAS1 is the least severe form of CAPS, MWS is intermediate in severity, and NOMID is the most severe form.\n\nThe signs and symptoms of CAPS affect multiple body systems. Generally, CAPS are characterized by periodic episodes of skin rash, fever, and joint pain. These episodes can be triggered by exposure to cold temperatures, fatigue, other stressors, or they may arise spontaneously. Episodes can last from a few hours to several days. These episodes typically begin in infancy or early childhood and persist throughout life.\n\nWhile the CAPS spectrum shares similar signs and symptoms, the individual conditions tend to have distinct patterns of features. People with FCAS1 are particularly sensitive to the cold, and exposure to cold temperatures can trigger a painful or burning rash. The rash usually affects the torso and limbs but may spread to the rest of the body. In addition to fever and joint pain, other possible symptoms include muscle aches, chills, drowsiness, eye redness, headache, and nausea.\n\nIndividuals with MWS develop the typical periodic episodes of skin rash, fever, and joint pain after cold exposure, although episodes may occur spontaneously or all the time. Additionally, they can develop progressive hearing loss in their teenage years. Other features of MWS include skin lesions or kidney damage from abnormal deposits of a protein called amyloid (amyloidosis).\n\nIn people with NOMID, the signs and symptoms of the condition are usually present from birth and persists throughout life. In addition to skin rash and fever, affected individuals may have joint inflammation, swelling, and joint deformities called contractures that may restrict movement. People with NOMID typically have headaches, seizures, and cognitive impairment resulting from chronic meningitis, which is inflammation of the tissue that covers and protects the brain and spinal cord (meninges). Other features of NOMID include eye problems, short stature, distinctive facial features, and kidney damage caused by amyloidosis.
Hyper-IgE recurrent infection syndrome 1, autosomal dominant
MedGen UID:
1648470
Concept ID:
C4721531
Disease or Syndrome
STAT3 hyper IgE syndrome (STAT3-HIES) is a primary immune deficiency syndrome characterized by elevated serum IgE, eczema, and recurrent skin and respiratory tract infections, together with several nonimmune features. This disorder typically manifests in the newborn period with a rash (often diagnosed as eosinophilic pustulosis) that subsequently evolves into an eczematoid dermatitis. Recurrent staphylococcal skin boils and bacterial pneumonias usually manifest in the first years of life. Pneumatoceles and bronchiectasis often result from aberrant healing of pneumonias. Mucocutaneous candidiasis is common. Nonimmune features may include retained primary teeth, scoliosis, bone fractures following minimal trauma, joint hyperextensibility, and characteristic facial appearance, which typically emerges in adolescence. Vascular abnormalities have been described and include middle-sized artery tortuosity and aneurysms, with infrequent clinical sequelae of myocardial infarction and subarachnoid hemorrhage. Gastrointestinal (GI) manifestations include gastroesophageal reflux disease, esophageal dysmotility, and spontaneous intestinal perforations (some of which are associated with diverticuli). Fungal infections of the GI tract (typically histoplasmosis, Cryptococcus, and Coccidioides) also occur infrequently. Survival is typically into adulthood, with most individuals now living into or past the sixth decade. Most deaths are associated with gram-negative (Pseudomonas) or filamentous fungal pneumonias resulting in hemoptysis. Lymphomas occur at an increased frequency.
Proteasome-associated autoinflammatory syndrome 3
MedGen UID:
1648456
Concept ID:
C4747850
Disease or Syndrome
Proteasome-associated autoinflammatory syndrome-3 is an autosomal recessive syndrome with onset in early infancy. Affected individuals present with nodular dermatitis, recurrent fever, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and dysregulation of the immune response, particularly associated with abnormal type I interferon-induced gene expression patterns. Additional features are highly variable, but may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications (summary by Brehm et al., 2015). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).
Proteasome-associated autoinflammatory syndrome 2
MedGen UID:
1648482
Concept ID:
C4747989
Disease or Syndrome
Proteasome-associated autoinflammatory syndrome-2 (PRAAS2) is an autosomal dominant disorder with onset in early infancy. Affected individuals develop severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency (summary by Poli et al., 2018). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).
Immunodeficiency 57
MedGen UID:
1648306
Concept ID:
C4748212
Disease or Syndrome
NAD(P)HX dehydratase deficiency
MedGen UID:
1681210
Concept ID:
C5193026
Disease or Syndrome
Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, and sometimes seizures, resulting in death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions (summary by Van Bergen et al., 2019). For a discussion of genetic heterogeneity of PEBEL, see PEBEL1 (617186).
Immunodeficiency 69
MedGen UID:
1735911
Concept ID:
C5436498
Disease or Syndrome
Immunodeficiency-69 (IMD69) is an autosomal recessive disorder characterized by increased susceptibility to disseminated mycobacterial infection, including after BCG (bacille Calmette-Guerin) vaccination. Affected individuals develop fever, hepatosplenomegaly, leukocytosis, and thrombocytosis during the acute infection. There appears to be normal immunologic function against other pathogens, including viruses and bacteria. Immunologic work-up shows normal parameters, but patient T and NK cells fail to produce gamma-interferon (IFNG) when stimulated in vitro (summary by Kerner et al., 2020). IMD69 is a form of mendelian susceptibility to mycobacterial disease (MSMD) (see, e.g., IMD27A; 209950).
Proteasome-associated autoinflammatory syndrome 5
MedGen UID:
1779962
Concept ID:
C5543027
Disease or Syndrome
Immunodeficiency 81
MedGen UID:
1788669
Concept ID:
C5543540
Disease or Syndrome
Immunodeficiency-81 (IMD81) is an autosomal recessive complex disorder with onset of recurrent infections, including fungal infections, in early infancy, associated with T-cell, neutrophil, and NK dysfunction. B cells may also show maturation abnormalities. Other features include autoimmune hemolytic anemia and abnormal platelet aggregation, indicating a complex disorder with a wide range of hematopoietic disturbances. The disorder is caused by a defect in intracellular signaling pathways (summary by Lev et al., 2021).
Immunodeficiency 82 with systemic inflammation
MedGen UID:
1781752
Concept ID:
C5543581
Disease or Syndrome
Immunodeficiency-82 with systemic inflammation (IMD82) is a complex autosomal dominant immunologic disorder characterized by recurrent infections with various organisms, as well as noninfectious inflammation manifest as lymphocytic organ infiltration with gastritis, colitis, and lung, liver, CNS, or skin disease. One of the more common features is inflammation of the stomach and bowel. Most patients develop symptoms in infancy or early childhood; the severity is variable. There may be accompanying fever, elevated white blood cell count, decreased B cells, hypogammaglobulinemia, increased C-reactive protein (CRP; 123260), and a generalized hyperinflammatory state. Immunologic workup shows variable B- and T-cell abnormalities such as skewed subgroups. Patients have a propensity for the development of lymphoma, usually in adulthood. At the molecular level, the disorder results from a gain-of-function mutation that leads to constitutive and enhanced activation of the intracellular inflammatory signaling pathway. Treatment with SYK inhibitors rescued human cell abnormalities and resulted in clinical improvement in mice (Wang et al., 2021).
Autoinflammatory syndrome, familial, X-linked, Behcet-like 2
MedGen UID:
1808082
Concept ID:
C5575495
Disease or Syndrome
X-linked familial Behcet-like autoinflammatory syndrome-2 (AIFBL2) is an X-linked recessive disorder characterized by the onset of inflammatory symptoms in the first decade of life in male patients. Affected males often present with oral mucosal ulceration and skin inflammation. More variable features may include gastrointestinal ulceration, arthritis, recurrent fevers, and iron deficiency anemia. Laboratory studies are consistent with immune dysregulation manifest as increased inflammatory markers and variable immune cell abnormalities, such as decreased NK cells and low memory B cells. One patient presented with recurrent infections and immunodeficiency in addition to autoinflammation. The disorder results from a defect in ELF4, which normally acts as a negative regulator of inflammatory disease. Symptoms may respond to blockade of IL1 (see 147760) or TNFA (191160) (summary by Tyler et al., 2021 and Sun et al., 2022). For a discussion of genetic heterogeneity of AIFBL, see AIFBL1 (616744).
Immunodeficiency 105
MedGen UID:
1809425
Concept ID:
C5677005
Disease or Syndrome
Immunodeficiency-105 (IMD105) is an autosomal recessive disorder characterized by onset of recurrent infections in early infancy. Manifestations may include pneumonia, dermatitis, and lymphadenopathy. B-cell lymphoma was reported in 1 patient. Laboratory studies show decreased or absent numbers of nonfunctional T cells, normal or increased levels of B cells, hypogammaglobulinemia, and normal or low NK cells. The disorder is caused by a deficiency of transmembrane protein CD45 (PTPRC) on leukocytes, which plays an important role in T- and B-cell development (Cale et al., 1997; Kung et al., 2000). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive SCID, see 601457.

Professional guidelines

PubMed

Efthimiou P, Kontzias A, Hur P, Rodha K, Ramakrishna GS, Nakasato P
Semin Arthritis Rheum 2021 Aug;51(4):858-874. Epub 2021 Jun 13 doi: 10.1016/j.semarthrit.2021.06.004. PMID: 34175791
Vairo F, Haider N, Kock R, Ntoumi F, Ippolito G, Zumla A
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J Allergy Clin Immunol 2014 May;133(5):1270-7. doi: 10.1016/j.jaci.2014.02.036. PMID: 24766875

Recent clinical studies

Etiology

Hossain MB, Haldar Neer AH
Cancer Treat Res 2023;185:49-58. doi: 10.1007/978-3-031-27156-4_3. PMID: 37306903
Oddis CV, Aggarwal R
Nat Rev Rheumatol 2018 May;14(5):279-289. Epub 2018 Mar 29 doi: 10.1038/nrrheum.2018.42. PMID: 29593343
Galvão VR, Giavina-Bianchi P, Castells M
Curr Allergy Asthma Rep 2014 Aug;14(8):452. doi: 10.1007/s11882-014-0452-6. PMID: 24951238
Bernstein JA, Lang DM, Khan DA, Craig T, Dreyfus D, Hsieh F, Sheikh J, Weldon D, Zuraw B, Bernstein DI, Blessing-Moore J, Cox L, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller DE, Spector SL, Tilles SA, Wallace D
J Allergy Clin Immunol 2014 May;133(5):1270-7. doi: 10.1016/j.jaci.2014.02.036. PMID: 24766875
Ehrenfeld M
Best Pract Res Clin Rheumatol 2012 Feb;26(1):135-45. doi: 10.1016/j.berh.2012.01.002. PMID: 22424199

Diagnosis

Longfellow S, Monteiro C
Am Fam Physician 2023 Jun;107(6):649-650. PMID: 37327172
Patruno C, Napolitano M, Genco L, Passante M, Lacarrubba F, Noto M, Fabbrocini G
Ital J Dermatol Venerol 2023 Feb;158(1):21-25. doi: 10.23736/S2784-8671.23.07448-0. PMID: 36939499
Sreekanth R, Venugopal L, Arunkrishnan B, Chaturvedi S, Sundaram S
Trop Doct 2022 Jan;52(1):199-201. Epub 2021 Dec 23 doi: 10.1177/00494755211063268. PMID: 34939861
Mahendradas P, Kawali A, Luthra S, Srinivasan S, Curi AL, Maheswari S, Ksiaa I, Khairallah M
Indian J Ophthalmol 2020 Sep;68(9):1775-1786. doi: 10.4103/ijo.IJO_1352_20. PMID: 32823394Free PMC Article
Drago F, Ciccarese G, Gasparini G, Cogorno L, Javor S, Toniolo A, Broccolo F
Future Microbiol 2017 Feb;12:171-193. Epub 2016 Nov 14 doi: 10.2217/fmb-2016-0147. PMID: 27838923

Therapy

Hannon CW, McCourt C, Lima HC, Chen S, Bennett C
Cochrane Database Syst Rev 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2. PMID: 33687069Free PMC Article
Singh J, Antimisiaris MF
Epileptic Disord 2020 Aug 1;22(4):511-514. doi: 10.1684/epd.2020.1189. PMID: 32729550
Oddis CV, Aggarwal R
Nat Rev Rheumatol 2018 May;14(5):279-289. Epub 2018 Mar 29 doi: 10.1038/nrrheum.2018.42. PMID: 29593343
Köhnlein T, Windisch W, Köhler D, Drabik A, Geiseler J, Hartl S, Karg O, Laier-Groeneveld G, Nava S, Schönhofer B, Schucher B, Wegscheider K, Criée CP, Welte T
Lancet Respir Med 2014 Sep;2(9):698-705. Epub 2014 Jul 24 doi: 10.1016/S2213-2600(14)70153-5. PMID: 25066329
Cheer SM, Foster RH
Am J Clin Dermatol 2000 Sep-Oct;1(5):307-14; discussion 315-6. doi: 10.2165/00128071-200001050-00005. PMID: 11702321

Prognosis

Kantarjian H, Short NJ, Jain N, Sasaki K, Huang X, Haddad FG, Khouri I, DiNardo CD, Pemmaraju N, Wierda W, Garcia-Manero G, Kebriaei P, Garris R, Loghavi S, Jorgensen J, Kwari M, O'Brien S, Ravandi F, Jabbour E
Am J Hematol 2023 Mar;98(3):493-501. Epub 2023 Jan 4 doi: 10.1002/ajh.26816. PMID: 36600670
Izmirly P, Kim M, Friedman DM, Costedoat-Chalumeau N, Clancy R, Copel JA, Phoon CKL, Cuneo BF, Cohen RE, Robins K, Masson M, Wainwright BJ, Zahr N, Saxena A, Buyon JP
J Am Coll Cardiol 2020 Jul 21;76(3):292-302. doi: 10.1016/j.jacc.2020.05.045. PMID: 32674792Free PMC Article
Jabbour E, Short NJ, Ravandi F, Huang X, Daver N, DiNardo CD, Konopleva M, Pemmaraju N, Wierda W, Garcia-Manero G, Sasaki K, Cortes J, Garris R, Khoury JD, Jorgensen J, Jain N, Alvarez J, O'Brien S, Kantarjian H
Lancet Haematol 2018 Dec;5(12):e618-e627. doi: 10.1016/S2352-3026(18)30176-5. PMID: 30501869Free PMC Article
Rota PA, Moss WJ, Takeda M, de Swart RL, Thompson KM, Goodson JL
Nat Rev Dis Primers 2016 Jul 14;2:16049. doi: 10.1038/nrdp.2016.49. PMID: 27411684
Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S
Lancet Oncol 2016 Jun;17(6):738-746. Epub 2016 Apr 20 doi: 10.1016/S1470-2045(16)00150-9. PMID: 27108243

Clinical prediction guides

Mahendradas P, Kawali A, Luthra S, Srinivasan S, Curi AL, Maheswari S, Ksiaa I, Khairallah M
Indian J Ophthalmol 2020 Sep;68(9):1775-1786. doi: 10.4103/ijo.IJO_1352_20. PMID: 32823394Free PMC Article
Oddis CV, Aggarwal R
Nat Rev Rheumatol 2018 May;14(5):279-289. Epub 2018 Mar 29 doi: 10.1038/nrrheum.2018.42. PMID: 29593343
Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, Roujeau JC
Am J Med 2011 Jul;124(7):588-97. Epub 2011 May 17 doi: 10.1016/j.amjmed.2011.01.017. PMID: 21592453
Praga M, González E
Kidney Int 2010 Jun;77(11):956-61. Epub 2010 Mar 24 doi: 10.1038/ki.2010.89. PMID: 20336051
Cheer SM, Foster RH
Am J Clin Dermatol 2000 Sep-Oct;1(5):307-14; discussion 315-6. doi: 10.2165/00128071-200001050-00005. PMID: 11702321

Recent systematic reviews

Mazzara C, Milani GP, Lava SAG, Bianchetti MG, Gualco G, Simonetti GD, Camozzi P, Kottanattu L
Acta Paediatr 2022 May;111(5):935-939. Epub 2022 Feb 27 doi: 10.1111/apa.16300. PMID: 35178772Free PMC Article
Mashayekhi F, Seirafianpour F, Pour Mohammad A, Goodarzi A
Int J Clin Pract 2021 Dec;75(12):e14720. Epub 2021 Sep 28 doi: 10.1111/ijcp.14720. PMID: 34411409Free PMC Article
Hannon CW, McCourt C, Lima HC, Chen S, Bennett C
Cochrane Database Syst Rev 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2. PMID: 33687069Free PMC Article
Tandon N, Yadav SS
J Ethnopharmacol 2020 Jun 12;255:112768. Epub 2020 Mar 19 doi: 10.1016/j.jep.2020.112768. PMID: 32201301
Xiao Y, Gan L, Wang J, Luo M, Luo H
Cochrane Database Syst Rev 2015 Nov 18;2015(11):CD008781. doi: 10.1002/14651858.CD008781.pub3. PMID: 26580100Free PMC Article

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