Ulerythema 

Updated: May 23, 2019
Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

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] Ulerythema ophryogenes falls within the broader category of keratosis pilaris atrophicans.[5] It was suggested to link this category with lichen planopilaris under the rubric of an even broader grouping, lichenoid folliculitis.[6]

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.

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,[7] which could be viewed as a new rare syndrome.[8] 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[9] , in one survey 82% having the former and 44% the latter, out of 45 patients.[10]

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.[11, 12] Zouboulis et al even claim that the LAMA1 gene is involved[13] ; however, Klein et al propose a 12q deletion as the cause of the condition.[14] A patient with Noonan syndrome and ulerythema ophryogenes associated with an SOS1 mutation has been described.[15]  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,[16] of which ulerythema ophryogenes can be viewed as a subtype.

Epidemiology

Frequency

Worldwide incidence rates are not known.

Race

Individuals of all races can be affected.

Sex

This condition can affect males and females.

Age

Children and young adults are most commonly affected with this condition.

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.[17]

Patient Education

Young patients should be encouraged to live with this mild esthetic shortcoming.

 

Presentation

History

The parents usually note erythema and tiny keratotic papules on the lateral parts of the eyebrows during early childhood. Similar lesions may develop on the lateral aspects of the front and on the cheeks. Later, atrophy and loss of eyebrows may ensue. Sometimes, discrete follicular papules appear; follicular papules may also be present on the extensor sites of the arms and the thighs.

Physical Examination

Erythema with slight follicular hyperkeratosis appears on the cheeks and lateral aspects of the eyebrows. The scalp may also be involved. The affected areas may feel rough on delicate palpation.

A generalized facial erythema with scattered open and closed comedones and milia may be present. Rarely, similar lesions may be seen on the extensor surfaces of the arms and legs.

Hyperkeratotic follicular plugs with surrounding erythema that eventually evolves into coalescent follicular depressions in a honeycombed or worm-eaten pattern may be present in ulerythema of the cheeks, also known as atrophoderma vermiculatum. From the cheeks, ulerythema may extend to the ears and forehead.

The condition usually improves as the patient ages, but a loss of the lateral aspects of the eyebrows is possible, and scars may develop in the affected areas.

Complications

Scars may eventually develop at the sites of the hyperkeratotic papules.

 

DDx

Diagnostic Considerations

Differentiate the following:

  • Atrophoderma vermiculatum[18]

  • Keratosis pilaris atrophicans (ulerythema ophryogenes) and keratosis pilaris decalvans

  • Psoriasis, atopic dermatitis, pityriasis rubra pilaris, and ichthyosis vulgaris

  • Erythromelanosis follicularis faciei[19, 20]

  • Folliculotropic mycosis fungoides[21]

  • Nilotinib-induced keratosis pilaris‒like eruption[22]

Ulerythema is not always differentiated from keratosis pilaris, which is rather common in young women; keratosis pilaris commonly occurs on the extensor surfaces of the arms. Keratosis follicularis spinulosa decalvans mainly affects the scalp, but it should also be considered a differential diagnosis.

Pityriasis rubra pilaris and psoriasis may also require distinction. Although pityriasis rubra pilaris may be similar to psoriasis, important clinical symptoms of psoriasis are missing, including the whitish scales, the Auspitz sign, and the nail pitting. The tiny follicular yellow-red papules are a typical clinical sign of pityriasis rubra pilaris, thereby distinguishing it from psoriasis.

In small children, ulerythema must be differentiated from seborrhoic dermatitis and from atopic dermatitis.

Graham-Little syndrome, an unusual form of lichen planopilaris, characterized by the presence of cicatricial alopecia on the scalp, keratosis pilaris of the trunk and extremities, and noncicatricial hair loss of the pubis and axillae, sometimes requires distinction.[23]

Unilateral keratosis pilaris atrophicans faciei may mimic follicular mucinosis.[24]

Differential Diagnoses

 

Workup

Laboratory Studies

No laboratory test, except histopathologic examination, is diagnostic.

Histologic Findings

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.

Staging

Two stages may eventually be observed: an early stage characterized by follicular hyperkeratosis and a late stage with some evidence of fibrosis and atrophy.

 

Treatment

Medical Care

The disease often improves with age. The risk-benefit correlation does not support the use of systemic retinoids for the treatment of ulerythema ophryogenes.

Mild keratolytics, such as lactic acid 5%, urea 5%, or salicylic acid 2-5%, may be interchanged with cold creams, while low-potency corticosteroids may also be applied for short periods. Topical retinoid therapy may be worth trying.[25]

Sun protection creams are recommended when sun exposure is anticipated because frequent exposure to UV radiation exacerbates ulerythema ophryogenes. Local retinoids may not be effective.

Surgical Care

Successful treatment with carbon dioxide laser was reported in 2 patients, and the 585-nm pulsed dye lasers seemed efficient[26] ; however, in general, the treatment is rather unrewarding. Treatment with intense pulsed light may be worth considering.[27] Keratosis pilaris rubra and keratosis pilaris atrophicans faciei may be treated with good results using pulsed dye laser at 595-nm wavelength.[28]

Diet

No special diet is necessary.

Activity

Excessive sunlight should be avoided.

Prevention

Patients with ulerythema ophryogenes should not be exposed to the sun without UV protection.

Long-Term Monitoring

Regular checkups are recommended for patients with this condition.