Mid-dermal elastolysis with prothrombotic abnormalities: two cases.

Sir, Mid-dermal elastolysis (MDE) is an idiopathic condition, clinically characterized by well-circumscribed fine wrinkles and histologically by a selective loss of elastic tissue of the mid-dermis. The aetiology of MDE is not clear: in some cases the lesions appear after exposure to ultraviolet (UV) radiation and are confined to areas of UV exposure; an association with autoimmune disorders including systemic lupus erythematosus (LE), Hashimoto thyroiditis and rheumatoid arthritis is also reported.1,2 We describe two patients with MDE developing after sun exposure, who presented positive antinuclear antibodies (ANA) and a protein S deficiency. Patient 1. A 37-year-old woman presented with a 2-year history of hyperpigmentation with wrinkling that involved her abdomen. The patient reported thrombotic events in her family. Past history revealed a fetal loss when she was aged 35 years. Examination revealed a well-demarcated asymptomatic plaque on the abdomen where tiny patches of fine wrinkling, arranged parallel to the skin cleavage lines, were present Laboratory investigations were normal except for a coagulation test which revealed a protein S deficiency in duplicate samples; levels of protein C and homocysteine were normal. Autoimmunity tests revealed IgG-positive ANA at low titre (1/80), speckled pattern. Antiphospholipid antibodies, anti-Borrelia antibodies and lupus anticoagulant (LA) were negative. Skin biopsy revealed atrophy of the epidermis with a zone of light invagination of the epidermal profile. Stains for elastic fibres revealed areas of focal elastolysis in the mid-dermis (Fig. 1b). Direct immunofluorescence (DIF) was negative. Patient 2. A 33-year-old woman presented with a 10-year history of wrinkled patches spreading over the skin. Since their appearance, the lesions had extended to involve the back, arms and abdomen. Her medical history revealed Hashimoto thyroiditis. At clinical examination well-circumscribed fine wrinkled plaques, with a faint erythema, were observed. Blood tests showed no abnormalities except for slight leucopenia, a reduction of C3 and protein S deficiency in three consecutive samples. Protein C and homocysteine levels were within normal range. Antiphospholipid antibodies, LA test and test for Lyme disease were negative. IgG-positive ANA were positive, at a very low titre (1/40), with a speckled pattern. Skin biopsy showed an essentially undamaged epidermis and dermis. Orcein stain revealed the selective loss of elastic tissue in the mid-dermis, whereas elastic fibres in the papillary dermis and in the lower half of the reticular dermis appeared normal. DIF revealed granular deposits of IgM and C3 at the dermoepidermal junction and IgM and C3 in the superficial dermal vessels. MDE is a rare acquired elastolytic disorder observed by Shelley and Wood3 in 1977. It is characterized by a selective loss of elastic tissue limited to the mid-dermis. About 60 cases have been described in the literature. Clinically it is characterized by the presence of well-circumscribed fine wrinkling or perifollicular papular protrusions, but the two types of lesions may coexist.4 The pathogenesis is unknown. Several theories have been proposed including destruction of the elastic fibres secondary to actinic damage or due to inflammation that may be clinically obvious or subclinical.5 Recent studies provide evidence for an imbalance between metalloproteinase activity and inhibition of endogenous elastase.4 Our first patient noticed a spreading of the lesions after sunbathing, but confined only to the abdomen. This is in accordance with literature data reporting that MDE does not necessarily affect all sun-exposed areas.6 Our second patient observed skin changes that began after UV exposure. Patroi et al.4 report an association with the use of oral contraception but this may be only coincidental and not causative. Our first patient reported the use of combined oral contraceptives for 5 years whereas our second patient had never used oral contraception. A smoking habit is also considered a possible factor contributing to the onset of MDE;4 this was not the case in our patients. MDE has been described also in patients with autoimmune disorders and elevated autoantibodies,2 leading to the hypothesis that MDE may have an autoimmune basis.2,4–6 One of our patients had a history of Hashimoto thyroiditis, both patients presented ANA at low titres, and in the second patient DIF was positive for granular deposits of IgM and C3 at the dermoepidermal junction and in the superficial dermal vessels. However, the clinical appearance, the low titres of ANA, the absence of systemic symptoms and nontypical histopathology for LE excluded the diagnosis of LE. A prothrombotic state has been described in patients with anetoderma,7 but until now there have been no reports of it in MDE. Interestingly, we found a protein S deficiency in our two patients. In addition, one patient reported a fetal loss and thrombotic events in her family, while the other reported a protein S deficiency in her sister. Histopathologically, no vascular abnormalities were found in our two patients. Microthrombosis has been found in some patients with anetoderma and anticardiolipin antibodies, and these findings have led to the suggestion that ischaemia of dermal tissues may trigger degeneration of elastic tissue.8,9 In the same way as anetoderma has been regarded as a skin manifestation of antiphospholipid syndrome,10 MDE might be considered as a cutaneous expression of prothrombotic abnormalities. In fact, prothrombotic disorders such as protein S deficiency could act with a similar mechanism to induce an ischaemic process with consequent local imbalance of metalloproteinases and their inhibitors, leading to the destruction of elastic tissue.