Phacomatosis pigmentovascularis type II

ARTICLE

Phacomatosis pigmentovascularis (PPV) is a rare condition first described by Ota in 1947 [1]. This entity is characterized by the simultaneous occurrence of a pigmented and a vascular nevus. Classification is based on the type of pigmented nevus. Each type is subdivided into two subtypes: (a) when only cutaneous involvement is present, (b) when cutaneous and systemic disease are found. Two cases of PPV type II are reported herein. One of them is an unusual observation in which PPV is associated with an Arnold-Chiari malformation.

Case reports

Case 1

A 23 year-old Algerian man was referred to us for cutaneous vascular and pigmentary abnormalities. His parents were not consanguinous, and there was no family history of neurocutaneous disease. He was born with an extensive nevus flammeus involving the face, including the area of the first division of the trigeminal nerve on the right side. Lateral sides of the neck, thorax and both arms were also affected (Fig. 1). Examination revealed on upper part of the back, blue gray pigmentation unclearly delimited, evocative of aberrant mongolian spots (Fig. 2). A nevus anemicus was also noted on the right pectoral area (Fig. 1). Neurological and ophthalmological examinations were normal. There was no mental retardation, nor personal history of seizure.

Laboratory studies showed an increased erythrocyte count (5.3 10⁹/L) with normal haemoglobin concentration (14.3 g/dL) and microcytosis (mean corpuscular volume 79 10 ^­15 fL). Thalassemia was investigated by means of haemoglobin electrophoresis because of the Algerian origin of the patient. The following values were noted: HbA2 was increased (4.5%), HbA1 and HbF were normal (64% and 1.5% respectively) leading to the diagnosis of minor beta thalassemia.

X-rays showed no abnormalities in the chest or bones. Encephalic MRI revealed an Arnold-Chiari malformation type I, characterized by a low position of the bulboprotuberancial junction and cerebellous tonsils, hydrocephalia, and cervical syringomyelia (Fig. 3). Some abnormalities were also noted in the cranium: diploë enlargement of the fronto-parietal and occipital areas together with an erosion of the skull bone of the left frontal area, filled by a brain hernia (Fig. 4). All these findings were asymptomatic.

Case 2

The second patient was a 30-year-old Italian woman with no neurocutaneous disease in her family history. She presented with an extensive congenital nevus flammeus involving the thorax, left arm, back (Fig. 5), and lower limbs (Fig. 6). Blue-black macular pigmentation was seen on periorbital areas, involving upper and lower eyelids of both eyes (Fig. 7). This discoloration was also present on the sclera, and the right shoulder. Nevus anemicus was associated with these cutaneous abnormalities on the right pectoral area. Childhood growth and development were normal, and there was no history of seizure. X-ray investigations of the chest and bones, arterio-venous ultrasound examination of the limbs, and encephalic MRI were all normal. Ophthalmologic examination showed bilateral scleral melanosis, without any other abnormalities.

Discussion

The distinctive association of vascular cutaneous malformations with pigmentary nevi was first discribed by Ota et al. [1], who proposed the term "phacomatosis pigmentovascularis". Four types were classified by Hasegawa et al. They also proposed dividing the classification into localized (a) or systemic (b) forms, whether it was associated or not with visceral involvement [2, 3]. Nevus anemicus can be an additional feature in types II, III, and IV (Table I).

More than eighty cases of PPV have been reported in the literature, most of them being Japanese patients. This disorder is also more frequent in Mediterranean and Indian people, and is exceptional in black people [4, 5]. Type II is the most frequently reported type (80%). Type III and IV of PPV are rare; only a few cases are described in the literature. The real incidence of PPV is difficult to evaluate because most of cases without visceral involvement are rarely published. In a study of 306 new-borns, Prigent et al. emphasized the underestimation of PPV after observing three cases in children originating from Sri Lanka, and born into three different families [6].

In Hasegawa's classification, it is unclear if the term "nevus spilus" refers to a uniformly pigmented macular lesion as originally described [7], or if it is considered as "spots on a spot", also called "speckled lentiginous nevus" [8]. It seems that in Japanese literature, this lesion is a uniformly pigmented macule ("tache café au lait"). On the other hand, cases of PPV recently reported with "nevus spilus" involve patients with extensive "spots on a spot" [9, 10]. It might be necessary to clarify the terminology, and we suggest that the term "nevus spilus" should be replaced by either "spots on a spot" or "café au lait spot". In such conditions, classification can be discussed: type III of PPV may correspond to an association of nevus flammeus with "spots on a spot", with or without nevus anemicus. Type IV would be a type III with aberrant mongolian spot. A new type (type V) of PPV could be introduced in this classification, defined by "café au lait spot", nevus flammeus with or without nevus anemicus. These findings have practical interest because malignant transformation of "spots on a spot" may occur, so patients with type III and IV of PPV should be kept under regular observation [11].

Visceral involvement is present in half of the cases of types II, III and IV, most of them being characterized by a complex angiodysplasia as Klippel-Trenaunay or/and Sturge-Weber syndrome. There is no report of systemic involvement in type I. It is not clear whether some patients presenting with others visceral abnormalities could be include in the "b" subtype. For example, a Japanese girl with nevus flammeus, extensive nevus spilus, aberrant mongolian spots and colonic polyposis has been described [12]. An East Indian child with Klippel-Trenaunay and Sturge-Weber syndrome, extensive mongolian spots, hypoplastic larynx and subglottic stenosis has been reported [13]. A selective IgA deficiency was also noted in a child with PPV type IIb [14]. Kaise et al. described a case of PPV accompanied by oesophageal varices due to hypoplasia of the portal veins [15]. These various conditions may represent incidental findings, or possible associations.

Various ophthalmologic manifestations have been described in PPV: vascular abnormalities can be present, as in Sturge-Weber syndrome (retinal, choroidal or iris hemangiomas, glaucoma, buphthalmos). Pigmentary disorders such as scleral melanosis, nevus of Ota and nevus of Ito are also frequently reported, as in our second patient. In the general population, only 5 to 10% present a bilateral nevus of Ota. By contrast, in PPV, patients with ocular pigmentary disorders more often than not have bilateral features. The complications of nevus of Ota are glaucoma and melanoma. Malignant transformation has been reported in more than 60 cases [16]. This is the reason why ophthalmological examination in these patients must be performed.

Except for vascular and pigmentary disorders, other ophthalmologic abnormalities may occur. Three cases of multiple iris hamartomas have been reported in patients with PPV type IIb: a 5-year-old girl with bilateral scleral melanosis and iris hamartomas [17], a 5-year-old girl with glaucoma, bilateral melanosis oculi and iris mammillations that were initially thought to be Lisch nodules [18], and a 2-year-old Brazilian boy with seizures and iris nodules [19].

In our first patient, the cranial abnormalities, particularly the diploë enlargment and the skull bone defect with brain hernia are unlikely to be related to PPV. Indeed, these findings may be observed in patients affected by thalassemia [20], as was our patient in whom a minor beta thalassemia was discovered.

Arnold-Chiari malformation has, to our knowledge, never been described with PPV. This congenital hindbrain deformity results from embryological alterations occurring during the fourth week of gestation, and affecting closure of the neural tube [21].

The pathogenesis of PPV remains controversial. Embryogenesis alterations occurring at the end of the first month of gestation, and affecting melanocytic migration and vascular development have been proposed [22]. Recently, the genetic concept of twin spots to explain the association of vascular and pigmentary abnormalities has been suggested: two different recessive mutations could be present on each chromosome of the same pair, on different loci, one for the pigmented lesions and the other for the vascular lesions. The embryo having each mutation in the heterozygous state has no clinical manifestation. But during embryogenesis, some somatic crossing over could occur with a mitotic recombination, resulting in homozygous cell populations in different areas leading to a mongolian spot or a nevus flammeus [23]. The fact that PPV and Arnold-Chiari malformation both result from disturbances occurring during the same embryological period leads us to think that this association is not coincidental.

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