Case reports of incontinentia pigmenti in males.

Incontinentia pigmenti is an X-linked dominant disorder, which is fatal in males, and majority of cases reported are in females. Here, we report 2 cases of males with incontinentia pigmenti. Case 1 has progressed through the classical stages of IP, giving history of vesicular and verrucous lesions and has presented with hyperpigmentation in whorled pattern. Case 2 has vesicular lesions in a linear distribution on the legs along with classical histopathological findings.

What was known?

Incontinentia pigmenti is a X linked dominant disorder seen mainly in females and is fatal in males.

Introduction

Incontinentia pigmenti (Bloch Sulzberger syndrome), a rare, hereditary syndrome inherited by X-linked dominant gene, primarily affects female infants and is lethal in males.[1] The IP gene has been mapped to Xq28, which encodes nuclear factor B essential modulator (NEMO).[2] The clinical manifestations include vesicular, verrucous, and peculiar swirled, pigmented cutaneous lesions sequentially. Associated findings include developmental defects of eyes (cataract, uveitis, optic atrophy, strabismus, retrolental fibroplasia), teeth (delayed dentition, partial anodontia, cone- or peg-shaped teeth, or absence of teeth), skeletal system (skull and palatal defects), and central nervous system (epilepsy, microcephaly, mental retardation, and slow motor development).[3] Cutaneous lesions may also be accompanied by defects of cutaneous appendages in the form of cicatricial alopecia or small and dystrophic nails.[4] Lesions may be seen either at birth or before the end of first week. Rarely, skin lesions start appearing after first 2 months of birth. Brownish, bluish-grey, or slaty pigmentation in characteristically diagnostic, bizarre, splashed or ‘Chinese figure’ distribution may persist for many years.

Diagnostic criteria for incontinentia pigmenti include:

Major criteria: (1) typical neonatal vesicular rash with eosinophilia; (2) typical blaschkoid hyperpigmentation on the trunk, fading in adolescence; and (3) linear, atrophic hairless lesions.

Minor criteria: (1) dental anomalies, (2) alopecia, (3) wooly hair, and (4) abnormal nails.

With a definitive family history, the presence of any major criterion strongly supports the diagnosis of incontinentia pigmenti.[5] In the absence of a family history, the presence of at least 1 major criterion is necessary. The presence of minor criteria supports the diagnosis of incontinentia pigmenti.

Case Reports

Case 1

A 5-years-old Muslim male child presented with cutaneous hyperpigmentation on trunk, extremities, and face.

The boy was an only child, born to third degree consanguineous parents with full-term normal delivery. There was no history of abortion or death of a male child previously. Family history was non-conclusive.

As informed by mother, the skin lesions started appearing at 1 week of age in the form of vesicular lesions on the lower extremities, which gradually spread onto the trunk. These were followed by crusted plaques, which healed with hyperpigmentation.

On examination, the child had slate brown hyperpigmented macules on face and lower limbs in linear distribution. Widely distributed areas of pigmentation in whorled pattern were seen on trunk [Figure 1]. Oral cavity showed hypodontia with peg-shaped teeth [Figure 2]. The physical and intellectual development of boy was considered subnormal for age by pediatrician. His developmental milestones were delayed for age, and he had complaints of primary nocturnal enueresis. Systemic examination including ocular, central nervous system (CNS), and skeletal systems revealed nothing abnormal. Hair and nails were normal. Hematological tests showed peripheral blood eosinophilia. CT scan brain was normal. 2D Echo revealed patent ductus arteriosus.

Figure 1

Whorled pattern of hyperpigmentation on trunk in case 1

Figure 2

Hypodontia with peg-shaped teeth in case 1

Histopathological examination revealed mild epidermal hyperplasia (acanthotic) with dyskeratotic cells with few whorls of squamous cells with central keratinization. Dermis reveals infiltrates of eosinophils and mononuclear cells.

Case 2

A 20-days-old male child, second in order, born to non-consanguineous parents, with an uneventful normal vaginal delivery, was brought with the complaints of vesiculobullous eruptions on both lower limbs [Figures 3] and 4] and right arm since birth. The other sibling was a male child who expired at 7 months of gestational age due to hydrops fetalis. On examination, the child had vesiculo-bullous lesions on both lower limbs. Hair and nails were normal.

Figure 3

Vesicular lesions on lower limbs in case 2

Figure 4

Vesicular lesions on lower limbs in case 2

The infectious causes were excluded (Tzanck test showed no giant cells, and test for antibodies for HSV, VZV was negative). Systemic examination including that of eyes, CNS, and skeletal system revealed nothing abnormal. Routine blood, urine, and stool examinations did not show any abnormality, except for raised eosinophils on differential leukocyte count. VDRL of mother and the child was non-reactive, and a skin biopsy was performed, which revealed spongiotic intra-epidermal vesicles with a rich eosinophil infiltrate [Figure 5].

Figure 5

Histopathology showing eosinophilic spongiosis and acanthosis in high power

Discussion

Incontinentia pigmenti is a rare genodermatoses with only few cases having been reported. Skin manifestations can be observed at birth or within neonatal period. Therefore, the role of dermatologists and pediatrician is crucial in early diagnosis of IP. Identification of male patients[6] is valuable because of their rarity. In our case, both patients had characteristic clinical features of the disease but were otherwise normal, which shows that both were suffering from mild variant of the disease, which belies the fact that the disease is lethal in males. Case 1 showed characteristic cutaneous whorled pigmentation with peg-shaped teeth and CVS abnormality. The diagnosis was further confirmed by hematological and histopathological findings. Case 2 had classical vesicular lesions, which were further confirmed by histopathology. Histopathology showed spongiosis with characteristic eosinophilic infiltrates. This disease being incurable, genetic counseling is an important aspect of management, which helps to reduce the disease burden on the family and the society. There is no specific test for incontinentia pigmenti, although genetic testing and DNA analysis can detect the genetic disorder on the X chromosome.

What is new?

We report 2 cases of Incontinentia pigmenti in males who exhibit mild variant of the disease and hence this article belies the fact that this disease is fatal in males.