Anetoderma, which was first described by Jadassohn in 1892, is characterized by localized areas of loss of substance and elastic tissue with flaccid skin and often leads to a herniation phenomenon [2
]. We could not find similar reports (other than anetoderma-like changes on distal extremities secondary to hamartomatous congenital melanocytic naevi) [4
] of anetoderma developing on distal extremities without involvement of the upper trunk and proximal arms, in the medical literature.
This rare disorder occurs mainly in women aged 20–40 years, but is occasionally reported in younger and older patients of both sexes. It is perhaps more frequent in central Europe than elsewhere, which suggests a possible relationship to chronic atrophic acrodermatitis (due to Borrelia
species) in some cases. In the most usual form, crops of round or oval, pink macules 0.5–1 centimeter in diameter develop on trunk, thighs and upper arms, less commonly on the neck and face and rarely elsewhere[3
]. The scalp, palms and soles are usually spared. Each macule extends for a week or two to reach the size of 2–3 centimeter [3
]. Sometimes there are larger plaques of erythema, and nodules have also been reported as primary lesion [5
]. The number of lesions varies widely, from less than five to one hundred or more [3
]. The lesions remain unchanged throughout life, and new lesions often continue to develop for many years. If the lesions coalesce, they form large atrophic areas, which are indistinguishable from acquired cutis laxa [3
]. They may become confluent, to cover large areas, especially at the roots of the limbs and on the neck [3
Although infrequently reported, anetoderma may occur in families, and patient must be examined for associated systemic abnormalities for thorough assessment of their skin disorders. In familial anetoderma, there were associated ocular, gastrointestinal or orthopedic anomalies in the affected patients or in any other family members, but causes without them have been reported [8
]. Although isolated and perhaps coincidental, these abnormalities could be related to the same process that produces the lesions of anetoderma [3
Primary anetoderma can be inherited, but it has also been described in association with prematurity, lupus erythematosus, antiphospholipid syndrome, and with decreased serum levels of alpha-1-antitrypsin [6
] and [11
]. Secondary anetoderma develops over other dermatoses are shown in Table .
Dermatoses Associated with Anetoderma
The differential diagnosis of anetoderma includes other focal dermal atrophies and miscellaneous diseases that must be differentiated from the skin herniation phenomenon of anetoderma [12
], are shown in Table .
Differential Diagnosis of Anetoderma [12-16]
Atrophoderma of Pasini and Pierini is a major source of confusion both etymologically and clinically. Patients have larger lesions with a sharp peripheral border dropping into a depression with no outpouching. On biopsy, elastin is normal, while collagen may be thickened, but this finding is difficult to quantify [12
]. Perifollicular atrophoderma is most prominent on the dorsa of the hands and often is associated with multiple basal cell carcinomas and hair abnormalities in the Bazex syndrome [13
]. Perifollicular atrophy also has been described in extreme forms of keratosis pilaris, in which large keratin plugs may produce a dilated patulous follicle. This condition usually found on the cheeks of young children. Both of these lesions mimic perifollicular anetoderma but lack elastin changes [12
]. In focal dermal hypoplasia thinning or absence of dermis, rather than changes in elastin fibres, accounts for the proximity of the subcutis to the epidermis [12
]. Cutis laxa, postinflammatory elastolysis [14
], and mid-dermal elastolysis [15
] share with anetoderma the property of cryptogenic loss of elastic fibres.
Elastase-producing strains of staphylococcus epidermidis have been held responsible for perifollicular macular atrophy. Anetoderma has also been reported in 5 patients with false-positive syphilis serology, 3 of who also fulfilled the criteria for the antiphospholipid syndrome [29
]. Its pathogenesis is not yet clearly established, but immunological mechanisms could play an important role in dermal elastolysis [35
]. The association of primary anetoderma with decreased levels of alpha-1-antitrypsin may be of significance: Alpha-1-antitrypsin inhibits neutrophil elastase and its reduction may cause increased elastic activity and elastin breakdown. Phagocytosis of elastic fibres by macrophages has been found in primary anetoderma [36
]. No antibodies have been demonstrated against elastic fibres [37
Venencie et al. [38
], suggested that the degradation of elastic fibres in patients with anetoderma is caused by enhanced expression of progelatinases A and B and production of the activated form of gelatinase A, and that the lack of control of these enzymes by tissue inhibitors of metalloproteinases is probably a key factor in the development and duration of anetodermic lesions.
Ghomrasseni et al. [39
], demonstrated that for the five samples of anetodermic skin, matrix metalloproteinase-1 (MMP-1) levels were significantly higher compared with the uninvolver cultures and the healthy samples. A significant increase of tissue inhibitors of metalloproteinase (TIMP-1) expression was also observed in the affected cultures of explants. The study demonstrated a significant increase in the production of gelatinase A (MMP-2), and no significant production of TIMP-2 in lesional skin compared with the samples from the two healthy donors.
Penicillamine-induced anetoderma has also been reported [3
] and [40
]. Penicillin and the antifibrinolytic drug ε-aminocaproic acid have been advocated [41
], but Venencie et al. [3
] studied 16 patients and found that no treatment was beneficial once the atrophy had developed. However, the wrinkled skin appearance in our patient had been present for 2 years, and his lesions did not show any signs of inflammation or pre-existing conditions like melanocytic naevi.