CHILD nevi comprise the cutaneous manifestations typical of CHILD syndrome, an acronym for Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defect, a rare, X-linked dominant genetic disease, lethal to males, resulting from mutations in the NSDHL gene, which belongs to the cholesterol biosynthesis pathway.1

Altered cholesterol biosynthesis affects myelin formation and organogenesis, resulting in neurological, skeletal, and visceral malformations.2,3 CHILD nevi arise as a physiological compensation for the lipid-poor and inflamed skin barrier due to the accumulation of its precursors, resulting in erythematous-squamous plaques that follow Blaschko's lines, with a predilection for fold areas, associated with pruritus and recurrent skin infections, which affects quality of life and represents a potential life-threatening risk.1,4

Laboratory tests are usually normal, and histopathological examination of CHILD nevi reveals nonspecific psoriasiform changes, which are useful for ruling out differential diagnoses. Clinical evaluation and, when available, genetic testing confirm the diagnosis.1

The first treatments used for CHILD nevi were topical keratolytic agents, emollients, corticosteroids, and calcineurin inhibitors, oral retinoids or methotrexate, showing unsatisfactory results, in addition to representing risks inherent to prolonged use and in potentially fertile patients.5 Therapeutic proposals based on the disease pathogenesis provide more satisfactory results and include the topical association of cholesterol with statins, aiming to replace the deficient lipid while inhibiting an initial phase of cholesterol biosynthesis, preventing the accumulation of potentially toxic sterols and other mediators.6–9

The present case describes the long-term follow-up (1 to 23 years) of five female patients with CHILD Syndrome in the Pediatric Dermatology outpatient clinic of Hospital das Clínicas, Faculty of Medicine, Universidade de São Paulo, Brazil.

All five cases had CHILD nevi, with pruritus and recurrent infections, which improved when the lesions became thinner and less inflamed. Ipsilateral limbs' hypoplasia with CHILD nevi was the rule; in Case 5, there was aplasia of the right upper limb. Three of the five patients have the left side affected (1, 3, and 4), with cases 1 and 3 having more associated malformations (Table 1). Studies suggest that the right side is more affected (7/3 ratio), but patients with left-sided involvement tend to have a worse prognosis, as visceral abnormalities are more common.1,2,4

The two longest-standing patients in the follow-up (Cases 1 and 2) used topical keratolytic agents (10% urea, occlusive salicylic acid), emollients, and calcipotriol at the beginning of treatment, with an unsatisfactory therapeutic response. Cutaneous therapy with lovastatin and cholesterol showed a satisfactory response in four of the five patients.

The average time required to obtain a satisfactory response with therapy based on the disease pathogenesis was two months, with daily use at the beginning of treatment (Fig. 1), which could be reduced to two or three times a week when the skin became thin and less inflamed. A satisfactory response was considered to be the thinning of the CHILD nevi, the reduction of pruritus and abrasions that predispose to infections, also facilitating adaptation for the use of prostheses in hypoplastic limbs, in addition to a reported improvement in quality of life.

Fig. 1.

CHILD nevus, showing Blaschkoid lesion in fold area of ​​a newborn patient (a) without treatment (b) after two months of use of topical 2% Simvastatin + 2% Cholesterol.

Loss of efficacy was observed over the years, a fact not yet described, without improvement with the association of keratolytic agents or calcipotriol. Observing the principle of potency of pharmacological action of statins,10 lovastatin was replaced with other drugs with more potent action, such as 2% simvastatin and then 2% atorvastatin, when loss of efficacy was identified during follow-up and therapeutic response was re-established. Case 1 was treated with Lovastatin and then switched to Simvastatin, temporarily stabilized, but continues with irregular treatment and recrudescence of lesions. Case 2 required a third formulation, atorvastatin (Fig. 2). Case 3 has remained stable with lovastatin alone for eight years. Cases 4 and 5 were started with simvastatin, are stable, and also satisfied with the obtained results.

Fig. 2.

CHILD nevus on the right lower limb associated with dysplasia. (a) Recurring lesion after nine years of use of 2% Lovastatin + 2% cholesterol. (b) Partial improvement with replacement with 2% simvastatin + 2% cholesterol. (c) Significant improvement after replacement with topical 2% atorvastatin + 2% cholesterol.

Studies with larger sample sizes and long-term follow-up are needed to understand clinical evolution and establish effective therapeutic guidelines. This is the first publication with long-term follow-up of CHILD nevus treatment with statins, focusing on the long-term loss of response to the less potent lovastatin, and subsequent re-establishment of response with the use of topical simvastatin and atorvastatin, with satisfactory results for the patients.