A rare, genetic, chronic, recurrent, slowly progressive, epidermal disease characterized by small, sterile, pustular eruptions, involving the nails and surrounding skin of the fingers and/or toes, which coalesce and burst, leaving erythematous, atrophic skin where new pustules develop. Onychodystrophy is frequently associated and anonychia and osteolysis are reported in severe cases. Local expansion (to involve the hands, forearms and/or feet) and involvement of mucosal surfaces (e.g. conjunctiva, tongue, urethra) may be observed.

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.

Any neonatal inflammatory skin and bowel disease in which the cause of the disease is a mutation in the ADAM17 gene.

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).

Neonatal nephrocutaneous inflammatory syndrome (NNCIS) is an autosomal recessive disorder characterized by intrauterine growth retardation and premature birth, fragile infection-prone skin, and nephromegaly with tubular dysfunction. Some patients have chronic diarrhea, and necrotizing enterocolitis with intestinal perforation has been observed. Other features include facial dysmorphisms and cardiac anomalies. Most patients require ventilatory and circulatory support at birth, exhibit failure to thrive, experience recurrent infections with sepsis as a common complication, and die within 6 months (Mazurova et al., 2020; Labbouz et al., 2023). Reviews Takeichi and Akiyama (2021) reviewed published reports of patients with mutation in the EGFR gene, whose features included intrauterine growth restriction; thin, translucent, and fragile skin (14 of 15 cases); skin desquamation (10 of 17 cases); ichthyosis (9 of 17 cases); recurrent skin infections and sepsis (9 of 12 cases); nephromegaly (10 of 16 cases); and congenital heart defects (7 of 17 cases). Other observed features included erythroderma, tubulopathy, necrotizing enterocolitis/intestinal perforation, cryptorchidism, hyperimmunoglobulin E, and dentinogenesis imperfecta. Almost all children died within 2.5 years after birth. The authors suggested that EGFR-associated systemic inflammatory diseases should be considered a part of the clinical spectrum of 'autoinflammatory keratinization diseases' (AiKDs).

Immunodeficiency-51 (IMD51) is an autosomal recessive primary immune deficiency that is usually characterized by onset of chronic mucocutaneous candidiasis in the first years of life. Most patients also show recurrent Staphylococcal skin infections, and may show increased susceptibility to chronic bacterial respiratory infections. Patient cells show a lack of cellular responses to stimulation with certain IL17 isoforms, including IL17A (603149), IL17F (606496), IL17A/F, and IL17E (IL25; 605658) (summary by Levy et al., 2016).

Immunodeficiency-66 (IMD66) is an autosomal recessive primary immune disorder caused by defective immune cell migration and chemotaxis resulting from defects in cytoskeletal actin dynamics. Neutrophils are primarily affected, although there may be defects in dendritic cells and T and B cells. The phenotype is characterized by onset of recurrent bacterial infections in infancy. Laboratory studies show normal levels of myeloid and lymphoid cells, but there may be mild thrombocytopenia (summary by Record et al., 2015).