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Xeroderma pigmentosum in three consecutive siblings of a Nigerian family: observations on oculocutaneous manifestations in black African children
  1. HAMIDU AHMED
  1. Department of Paediatrics, Usmanu Danfodiyo University, Teaching Hospital, PMB 2370, Sokoto, Nigeria
  2. UDUTH, Sokoto, Nigeria
  3. University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
  1. RAHMATU Y HASSAN
  1. Department of Paediatrics, Usmanu Danfodiyo University, Teaching Hospital, PMB 2370, Sokoto, Nigeria
  2. UDUTH, Sokoto, Nigeria
  3. University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
  1. UMAR H PINDIGA
  1. Department of Paediatrics, Usmanu Danfodiyo University, Teaching Hospital, PMB 2370, Sokoto, Nigeria
  2. UDUTH, Sokoto, Nigeria
  3. University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
  1. Dr Ahmed

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Editor,—Xeroderma pigmentosum (XP), a rare autosomal recessive disorder characterised by defective DNA repair leading to clinical and cellular hypersensitivity to ultraviolet radiation, manifesting mainly as intolerance of skin and eyes to light, has been described in all races, but is exceedingly rare in the negroid race, although some cases have been reported in both the American and African black people.We describe three consecutive siblings of a Nigerian, Fulani, family with the typical features of XP. We wish to draw attention to the clinical, phenotypic variations of this syndrome in black children of the same family living together in an area of high sunshine, and the difficulties in the management of XP patients with advanced disease and limited access to facilities in an environment where avoidance of skin exposure to intense ultraviolet rays is problematic. We believe the patients we have described constitute the first series on XP in black children in the west African subregion.

CASE REPORTS

Case 1

The proband, a 9 year old girl, was first seen at Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto (13.02° N, 5.14° E), Nigeria, in February 1999 with a history of the development of generalised erythema of the skin of the limbs, face, and trunk from the age of 1 week, on exposure to sunshine, with the large red spots changing into dark lesions with blistering. This was followed by the development of photophobia from the age of 1½ years, skin lesions, comprising freckles, on limbs and face, hypopigmented and hyperpigmented lesions covering both sun exposed and covered areas of the skin with onset from age 2 years, relentless worsening of vision from the age of 2 years, and development of an ulcer on the right cheek at the age of 7½ years which had become persistent. The child was a product of a consanguineous marriage; the parents were of low socioeconomic class. The proband was the fifth in birth rank, in a monogamous family consisting of nine children aged between 5 months and 19 years. Two other siblings following the proband in birth sequence, the 6th and 7th, a 7 year old boy and a 5 year old girl, respectively, were also afflicted with a similar disease process involving the skin and eyes. Both parents were unaffected. On examination, the entire skin was dry (with the exception of the soles and palms) covered with a mixture of mottled, hyperpigmented and hypopigmented, atrophic roundish and oval macules, giving the entire skin a chequered appearance, associated with generalised actinic keratoses (manifesting on black skin as palpable, rough, blackish spots covered with adherent scales). These keratotic lesions were more numerous on the face. A large reddish ulcerated plaque (2 × 2 cm) with raised, dark, keratotic, sharply demarcated borders was seen on the right cheek and crusted ulceration on the nasal bridge was also noted. Biopsy of the ulcer on the cheek showed well differentiated squamous cell carcinoma. The following lesions were noted in the right eye. The skin of the lids was covered by similar lesions as elsewhere on the skin. The lower lid margin was ulcerated. A conjunctival mass 0.5 × 0.75 cm extended from the medial canthus to and covered the 2–5 o'clock of the limbus. The rest of the limbus was obliterated by a dark, flat lesion. The cornea was hazy because of a fibrovascular membrane on its epithelial surface making it impossible to view structures deeper to it. The left eye also showed loss of all eyelashes of the lower lid and most of those in the upper lid. A large nodular conjunctival lesion (1.5 cm × 1 cm) occupied the whole of the temporal conjunctiva and two thirds of the adjacent cornea. This lesion was pink, firm but friable (see Fig 1). The visual acuity (VA) was perception of light (PL), in the right eye and nil perception of light (NPL), in the left. Biopsy of the conjunctival mass LE showed a moderately differentiated squamous cell carcinoma. On the basis of the characteristic cutaneous and ocular lesions associated with sunshine hypersensitivity and histologically proved squamous cell carcinoma of both the skin and conjunctiva, the diagnosis in the proband was xeroderma pigmentosum in its final phase, the cancerous period.

Figure 1

Left eye of the proband demonstrating the large pink, friable conjunctival lesion, a biopsy of which showed moderately differentiated squamous cell carcinoma. Note the scaly nature of the surrounding facial skin with actinic keratotic lesions, hypopigmented and hyperpigmented areas and crusted ulceration of the nasal bridge, all typical cutaneous lesions in xeroderma pigmentosum.

Case 2

This 7 year old boy, the brother of the proband, presented with milder symptoms of XP, with slower progression. Thus, the initial generalised erythematous rash associated with exposure to sunshine became obvious from the age of 3 months; worsening of vision developed from the age of 4 years. The cutaneous lesions, though similar to those in the proband, were less severe. The entire skin was also dry, covered with hyperpigmented and hypopigmented atrophic roundish lesions. The actinic keratotic lesions were less numerous. There were no ulcerations and no cutaneous tumours. The ocular lesions were also milder than in the proband. In the right eye the conjunctiva was xerotic, but without areas of hypertrophy. The cornea was dull, but clear with tendency to dryness. The left eye showed total loss of lashes of the lower lid and hypertrophy of the nasal half of the conjunctiva, with raising of its edge towards the limbus. The VA (6/60 in both eyes) was better than in the proband. The ocular and cutaneous lesions were compatible with xeroderma pigmentosum in the precancerous phase

Case 3

This was the 5 year old sister of the proband. The onset of the disease and its severity took a middle course between that of the index case (case 1) and the second patient. The onset of erythematous skin lesions and freckles following exposure to sunshine was at age 6 weeks. Hypopigmented and hyperpigmented macules become evident by the age of 2½ years. The actinic keratoses became numerous by age 3½ years and ulceration of the upper lip was noticed at age 4½ years. The worsening of vision became obvious from the age of 3 years. Ocular examination revealed marked blepharospasm in the right eye, the conjunctiva was generally fleshy, vascular, with a tendency to bleed and covered the cornea in both its nasal half and inferotemporal quadrant. Other corneal areas were covered by a fibrovascular epithelial membrane (Fig 2). Biopsy of the conjunctival mass reveal moderately differentiated squamous cell carcinoma. In the left eye there was total loss of eyelashes of the lower lid, and a vascular fleshy overgrowth of the conjunctiva covering the whole of the nasal one third of the cornea, and also a small area of the cornea temporally at about 3 o'clock. The VA in the left eye was limited to hand movement only at 2 metres while in the right eye it was PL only. The severity of actinic keratotic lesions was midway between that of the proband and case 2. Although there were crusty skin ulcers of the upper lip, there were no obvious cutaneous tumours. On the basis of the oculocutaneous lesions, associated with sunshine hypersensitivity and the similarity of the symptomatology with that found in the other two siblings, the diagnosis of xeroderma pigmentosum was not in doubt. The disease in this patient had also advanced to the cancerous phase.

Figure 2

Case 3, right eye showing vascular, fleshy conjunctival tissues, a biopsy of which revealed features consistent with moderately differentiated squamous cell carcinoma. The facial skin demonstrates actinic keratotic lesions typical of xeroderma pigmentosum.

COMMENT

XP is generally regarded as a very serious disease in the tropics because of its pronounced sensitivity to sunlight. There was some degree of variation in the severity and rate of progression of the disease in our patients despite their first degree relationship and the common environment characterised by high sunshine. The assertion that the severity of the skin and eye lesions relates more to the degree of skin exposure may not explain, entirely, this variation since all the affected children live in a common environment of high sunshine. A recent Japanese study has shown that there is correlation of the clinical manifestations and gene mutations even among patients of the same complementation group. We had no facilities in Nigeria to determine the complementation group of our patients and the individual gene mutations of these children. There are many obstacles in Nigeria to the proper management of XP patients in general and the three siblings we have described in particular. Firstly, an elaborate system of photoprotection from birth could not be carried out since there were no facilities for prenatal diagnosis of XP. Secondly, sun exposure could not be altogether avoided and only some measure of protection again the sun was provided—special glasses, clothes, and sunscreen creams. Unfortunately, the management of our patients was limited to these only. Surgical intervention could not be carried out mainly because the cost was too exorbitant for the poor parents. For these patients with advanced disease, limited access to facilities, in an environment of high sunshine, the prognosis is indeed gloomy.

References

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