Pseudoxanthoma elasticum with periumbilical perforation in a nullipara.

Pseudoxanthoma elasticum (PXE) is an inherited multisystem disorder that primarily affects the skin and is characterized by progressive calcification and degeneration of the elastic fibers. PXE has recently been found to be caused by mutations in the ATP-binding cassette transporter C6 (ABCC6) or the multidrug resistance-associated protein 6 (MRP6) genes. Perforating PXE is a rare presentation that is usually seen in the periumbilical area in obese multiparous black women; it has distinct clinical and histopathological features and there may or may not be systemic manifestations. We report an unusual case of PXE in a nulliparous woman, with perforation in the periumbilical area and without any systemic involvement.

Introduction

Pseudoxanthoma elasticum (PXE) or Grönblad-Strandberg syndrome is a multisystem disorder characterized by progressive calcification and degeneration of the elastic fibers throughout the body.[1] Perforating PXE is a rare variant that occurs either in association with hereditary PXE or as a localized acquired cutaneous form. We report a case of PXE with periumbilical perforation in a nulliparous woman without any systemic involvement.

Case Report

A 21-year-old nullipara presented with asymptomatic pigmented skin lesions over the sides of her neck and abdomen of 1 year duration. The onset was insidious, beginning over the sides of neck as a slight alteration in texture, and was not preceded by trauma or any general symptom such as fever. The patient had been married for 2 years. She had no history of abortion or any systemic complaints. Her family history was not contributory.

Her systemic examination was unremarkable; blood pressure and other vital signs were normal. Dermatologic examination revealed multiple brownish-black papules symmetrically distributed over the front and sides of the neck [Figure 1] and periumbilical area [Figure 2]. The skin over the area was soft, lax, and wrinkled. A few of the papules above the umbilicus were relatively keratotic. The rest of the skin was normal. The mucosa over the hard palate showed small, firm, yellowish-white plaques. Based on these findings we arrived at a clinical diagnosis of PXE.

Figure 1

Multiple brownish-black papules on the sides of the neck, with soft, lax, and wrinkled overlying skin

Figure 2

Multiple brownish-black papules with soft, lax, and wrinkled skin in the periumbilical area

Ocular examination did not reveal any abnormality. The routine hemogram and biochemical parameters, including renal function tests and serum calcium, were within normal limits; chest X-ray and EKG were also normal. The feces was negative for occult blood. Histology of the biopsy specimen showed fragmented, irregularly clumped, basophilic material throughout the mid-dermis [Figure 3]. The section from the periumbilical plaque showed discontinuity of the epidermis through which the elastic fibers were being extruded through this break in the epithelium [Figure 4].

Figure 3

Fragmented irregularly clumped basophilic material throughout the mid-dermis (H and E stain ×100)

Figure 4

Elimination of the altered elastic fiber through the epidermis (Verhoeff-van Gieson stain ×100)

The patient is being followed up and has been specifically instructed to report if she becomes pregnant.

Discussion

PXE is an elastic tissue disorder that is more common in females. Rigal first described the cutaneous lesions of PXE in 1881 and Darier was the first to demonstrate the typical histological changes in the elastic fibers. Recent studies show that PXE is caused by mutations in the ATP-binding cassette transporter C6 (ABCC6) gene,[23] which is also known as multidrug resistance-associated protein 6 (MRP6) gene.[4] The localized lesion usually occurs in a periumbilical location in obese multiparous black women, with or without accompanying systemic manifestations.[5] The usual age of onset remains unclear. Juvenile cases of PXE have been seen, with reports of the condition in a 2-year-old boy with microlithiasis of the testicle[6] and in an 8-year-old girl with ocular findings.[7]

The cutaneous manifestations of PXE are highly characteristic and are generally the first physical signs of the developing disorder. The characteristic cutaneous findings are small yellowish papules coalescing into plaques, presenting classically along the sides of the neck and giving rise to a ‘gooseflesh’ or ‘plucked chicken skin’ appearance. Other sites of predilection are the axillae, periumbilical area, groin, perineum, and thigh. These skin lesions are usually noted in the second or third decades of life. In older individuals the involved skin becomes lax and hangs in large folds. Other clinical presentations reported in literature include acneiform lesions, brown reticulate macules, and chronic granulomatous nodules.[8] Elastosis perforans serpiginosa may coexist with PXE. Of the systemic involvement, ocular manifestation as angioid streaks is the most frequent association. Periumbilical PXE has been reported to be associated with chronic renal failure and bilateral angioid streaks.[9] Many of the pathologic changes associated with PXE are irreversible.

Recently it has been reported that mild chronic oxidative stress affects PXE fibroblasts, which suggests that reactive oxygen scavengers might improve this disorder. Oxidative stress has also been reported to play an important role in the mechanism of the calcifications and hence in the pathogenesis of PXE.[10] The prognosis in PXE largely depends on the extent of extracutaneous organ involvement, and life expectancy depends on the system involvement and the complications if any. Pregnancy is not contraindicated in PXE patients, though the risk of miscarriage is increased in the first trimester. Patients typically have a normal life span, but complications such as acute gastrointestinal hemorrhage, myocardial infarction, or cerebral hemorrhage can be fatal.

Conclusion

It is known that damaged tissue is susceptible to calcium deposition in patients with hypercalcemia, which suggests that the elastic fiber alteration caused by high levels of reactive oxygen species leads to the calcification in PXE. To the best of our knowledge, PXE with periumbilical perforation without any systemic involvement has so far not been reported in a nulliparous woman. In addition to periodic screening to exclude abnormal phosphate–calcium metabolism or renal abnormalities, women with PXE should be thoroughly examined for any involvement of the periumbilical area and their pregnancy must be closely and carefully followed up.