Practice Essentials
Ulerythema ophryogenes, a rare cutaneous disorder, is characterized by inflammatory keratotic facial papules that may result in scars, atrophy, and alopecia. This disorder has been described in association with other congenital anomalies such as Noonan syndrome, de Lange syndrome, and Rubinstein-Taybi syndrome. [1, 2, 3, 4, 5] Ulerythema ophryogenes falls within the broader category of keratosis pilaris atrophicans. [6] It was suggested to link this category with lichen planopilaris under the rubric of an even broader grouping, lichenoid folliculitis. [7]
In 1889, Tancer introduced the term ulerythema ophryogenes. In 1892, Unna coined the term. In 1925, Gans used the designation keratosis pilaris rubra atrophicans faciei.
Prognosis
The disease tends to improve over time. However, this disorder may be the first sign of Noonan syndrome, which is important to recognize owing to its cardiovascular defects. [8]
Diagnostics
No laboratory test, except histopathologic examination, is diagnostic.
In the early phase, pilosebaceous follicles filled with keratotic plugs and a mild perifollicular inflammatory infiltrate are observed. Cystic dilatation of the hair follicles may be evident on the cheeks. Later, atrophy of both hair follicles and sebaceous glands, as well as a dermal fibrosis, may appear.
Two stages may eventually be observed: an early stage characterized by follicular hyperkeratosis and a late stage with some evidence of fibrosis and atrophy.
Pathophysiology
Ulerythema ophryogenes is a relatively infrequent disorder that mainly affects children and young adults. It is usually sporadic, although cases inherited in an autosomal dominant pattern also are described. Although the condition is benign, it is still worrisome for parents. The inclusion of ulerythema ophryogenes into the concept of pilar keratoses has been proposed. Griffiths proposes the inclusion into the broader concept of keratosis pilaris atrophicans, while Dawber proposes the inclusion into scarring follicular keratosis.
Genetic factors are important. There appears to be an association between the syndrome of partial monosomy of the short arm of chromosome 18 and the genodermatoses keratosis pilaris and ulerythema ophryogenes, [14] which could be viewed as a new rare syndrome. [15] A few patients have been described, suggesting this linkage. The genes responsible for follicular keratinization could be located on the short arm of this chromosome. Most patients with cardiofaciocutaneous syndrome exhibit keratosis pilaris and ulerythema ophryogenes [16] , in one survey 82% having the former and 44% the latter, out of 45 patients. [17]
Etiology
The true cause of ulerythema ophryogenes remains unknown. In a few families, this disorder is inherited in an autosomal dominant pattern. A molecular defect has so far not been elucidated, but certain clues are emerging as ulerythema appears as a trait in different syndromes.
Possible molecular defects are mentioned in ulerythema ophryogenes associated with more serious conditions such as Cornelia de Lange syndrome or Noonan syndrome, such as a deletion of the short arm of chromosome 18p caused by Y/18 translocation. [18, 19] Zouboulis et al even claim that the LAMA1 gene is involved [20] ; however, Klein et al propose a 12q deletion as the cause of the condition. [21] A patient with Noonan syndrome and ulerythema ophryogenes associated with an SOS1 mutation has been described. [22] Whole exome sequencing identified a unique homozygous missense variant on the lipoprotein receptor-related protein 1 gene as pathogenic, at least in cases of autosomal recessive keratosis pilaris atrophicans, [23] of which ulerythema ophryogenes can be viewed as a subtype.
Epidemiology
Worldwide incidence rates are not known. Individuals of all races can be affected. This condition can affect males and females. Children and young adults are most commonly affected with this condition.
