The diagnosis of MAP is based in the majority of the cases on the pathognomonic skin lesions. They are about 0.5-1 cm large papules with an atrophic porcelain-white centre and an erythematous, teleangiectatic rim mostly occurring on the trunk and the upper extremities [⁴,¹⁰] (Figures 1, 2). The lesions appear initially as small erythematous papules. After a few days the centre sinks and they start to demonstrate the characteristic morphology. Palms, soles, scalp and face are rarely involved. On the other hand, involvement of the internal organs, with multiple limited infarcts of the intestine and/or the central nervous system (CNS) as well as of other organs, such as the lungs (presenting as pleuritis and/or pericarditis) and the eyes, has also been reported [^11-14].

Due to the markedly different prognosis between the apparently idiopathic cutaneous disease and MAP with systemic involvement, the first variant - in contrast to the latter "malignant" one - has been termed "benign atrophic papulosis" by some authors [¹⁵,¹⁶]. However, it is still unclear if these two forms can be unambiguously distinguished from each other, since systemic involvement can develop year after the occurrence of the skin lesions.

The so called "benign" form of the disease is characterized by the typical skin lesions, which persist over years or lifelong, without involvement of the inner organs [¹⁷]. Several cases have exhibited signs of inheritance, especially between first-degree relatives [⁷,⁹]. The malignant variant is characterized by involvement of the skin and the inner organs, either occurring simultaneously or subsequently. The systemic manifestations can be followed in many cases by serious complications, namely bowel perforation and peritonitis as well as thrombosis of the cerebral arteries or massive cerebral hemorrhage, meningitis, encephalitis, radiculopathy, myelitis [¹⁸] leading to lethal course in approx. 50% of the patients within 2 to 3 years. Lung involvement can be followed by pleuritis and/or pericarditis [¹⁰,¹⁹,²⁰]. The prognosis can also be influenced by the extent of these ischemic complications, which are the determinants of mortality [²,⁸,²¹]. An ocular involvement with affection of the eyelids, conjuctiva, retina, sclera and the choroid plexus, as well as the development of diplopia and ophthalmoplegia as secondary side effects of the neurologic involvement have also been described [²²]. The fact that a systemic involvement can develop suddenly, years after the occurrence of skin lesions, makes a regular medical follow-up of the patients necessary.

The diagnosis of MAP is a clinical one and can be supported by the histological findings. The classical histology shows a wedge-shaped connective tissue necrosis, due to thrombotic occlusion of the small arteries deep in the corium [²⁰,²³,²⁴]. However, these characteristic features cannot be demonstrated in all cases [²⁵]. Harvell et al. [²⁶] examined in a case report the histology of the lesions according to the duration of their existence. Early lesions have shown a superficial and deep perivascular lymphocytic infiltration, with distinct mucin deposition, which resembled lupus erythematosus. The fully developed lesions had more prominent changes in the dermoepidermal junction, with atrophy of the epidermis and an area of sclerosis in the papillary dermis. These characteristics could be compatible with a minimal variant of lichen sclerosus et atrophicans. The late lesions showed a wedge-shaped necrosis, sparse lymphocytes and markedly less mucin deposition in comparison to the early and fully developed lesions (Figure 3).

No specific alterations of laboratory parameters - if any - have been reported [¹⁰] and no markers exist, which could verify the diagnosis. However, a relative large percentage of the patients has been described to present defects of blood coagulation.

The etiology of MAP remains unexplained. There is a whole series of hypotheses but none of them could be proven yet. The 3 most reasonable suggested hypotheses about the pathophysiology of the disease are vasculitis, coagulopathy and primary dysfunction of the endothelial cells [²⁷]. Although heterogeneous the aforementioned etiological suggestions are not necessarily mutually exclusive. The simultaneous presence of various factors creating the appropriate conditions for the development of thrombosis should be considered.

There is no uniformly effective therapy for MAP. Efforts with fibrinolytic and immunosuppressive therapeutic regimens like cyclosporine A, azathioprine, cyclophosphamide and corticosteroids have been mostly unsuccessful. Furthermore, there have been reported cases where MAP worsened during immunosupression [⁷,⁴⁶]. Explorative treatment with eculizumab could not prevent the development or progression of systemic manifestations (personal communications), despite its reported initial effectiveness on skin and intestinal lesions [⁴⁷,⁴⁸]. Other therapeutic efforts with anticoagulants and compounds that facilitate blood perfusion, such as acetylosalicylic acid (aspirin), pentoxifylline, dipyridamole, ticlodipine and heparin, have achieved a partial regression of the skin lesions in single cases [⁴,¹¹,²⁸,³⁴,³⁹,⁴⁹,⁵⁰]. Therefore, these agents can be used as a first therapeutic approach on a newly diagnosed patient with MAP. Subcutaneous treprostinil has currently been tested successfully in a case with eculizumab-resistant MAP with intestinal and CNS manifestations (Dr. Lee S. Shapiro, Albany, NY, personal communication).

Since every diagnosed MAP case can potentially develop into the systemic, life-threatening variant, an annual follow-up is mandatory. This should include a clinical inspection of the skin combined with additional examinations, such as brain magnetic resonance tomography, gastroscopy and colonoscopy, as well as X-ray of the chest and abdominal ultrasound in order to assess the long-term prognosis.