Epidemiological, clinical and laboratory profiles of cutaneous polyarteritis nodosa patients: Report of 22 cases and literature review

Highlights

• A retrospective review of 22 cases diagnosed as CPAN over the last 11 years was made.

• Ulcers and livedo racemosa were the most frequent cutaneous manifestations.

• Autoimmune, infectious and thrombophilic diseases should be investigated.

• No case of CPAN progressed to the systemic form of the disease.

Abstract

Cutaneous polyarteritis nodosa (CPAN) is a rare disease that affects small and middle caliber vessels of the deep dermis and subcutaneous tissue and its etiopathology remains yet to be understood. Methods: Retrospective review of twenty two cases diagnosed as CPAN and confirmed by skin biopsy over the last 11 years was evaluated in our department. Results: We found predominance in white woman, mean age of 39.4 years, showing no comorbidities in most of our sample. Mean follow-up time was 58 months. The most frequent cutaneous manifestations were ulcers, livedo racemosa, subcutaneous nodules, atrophie blanche lesions and purpuras; with lower limb involvement in all cases, however other areas were also involved. The main regional symptoms were pain and paresthesia, while systemic complaints were absent in the majority of cases. Mononeuritis multiplex was identified in a quarter of our sample. Most of the laboratory findings were non-specific. There was evidence for previous contact with Mycobacterium tuberculosis in 46.1% of cases which were tested for purified protein derivative (PPD) test. In our patients the disease course was benign and without complications, and systemic polyarteritis nodosa did not develop in any patient. Conclusions: An extensive work-up including laboratory tests on autoimmunity and thrombophilic factors and investigation of infectious diseases, especially previous contact with tuberculosis agent, should be part of the CPAN investigation.

Introduction

Classic polyarteritis nodosa (PAN) was the first systemic vasculitis described. In 1866, Kussmaul and Maier characterized this fatal condition, originally named “periarteritis nodosa”. In 1903, Ferrari pointed out the transmural nature of the arterial inflammation involving medium caliber vessels, leading him to propose the term “polyarteritis nodosa”. However, it was only in 1931 that Lindberg recognized the existence of a limited cutaneous form of PAN [1], [2].

Multi-organ involvement in systemic PAN is pervasive, particularly in the kidneys, heart and liver; although in most cases cutaneous findings are the first evidence of the disease. On the other hand, the cutaneous polyarteritis nodosa (CPAN), which affects predominantly the skin, could also be associated with extracutaneous findings and includes fever, malaise, myalgias, arthralgias and neuropathy. The distinction between the systemic and the cutaneous form is essential. The clinical course of CPAN is chronic, varying the number of remissions and relapses [3], [4], [5], [6], [7]. Its true incidence is to be yet accurately identified, affecting subjects that could be placed in all ages, ranging from infants to elderly individuals and affects predominantly women [1], [3], [4], [8].

The etiology involved in CPAN lingers in an uncertain ground, but current knowledge advocates that it is a disorder mediated by immune complexes. Direct immunofluorescence often shows IgM and C3 deposits within affected arterial walls [1], [8], [9]. Furthermore, a 77.8% prevalence of IgM antibodies against the phosphatidylserine–prothrombin complex among patients with CPAN helps to embed the theory that prothrombin bound for apoptotic endothelial cells induces an immune response. This process would, then, lead to the development of anti-phosphatidylserine–prothrombin complex antibodies, which, by its turn, presumably activates the classical complement pathway to cause CPAN [9].

A large number of infectious and non-infectious entities have been associated both to the beginning and the recurrence of CPAN. Among infectious agents, the one that plays the most frequent role is group A beta-hemolytic streptococcus, especially in children [10], [11], [12]. With its relation to hepatitis B and C, HIV, B19 parvovirus and Mycobacterium tuberculosis have been pointed out, among others [13], [14], [15], [16], [17], [18], [19].

In the context of non-infectious diseases, an association with autoimmune diseases has been pointed out, such as myasthenia gravis, Chron's disease, ulcerative retocolitis and auto-immune hepatitis [20], [21], [22], [23]. Still, other categories are listed apart like neoplasms, vena cava thrombosis and immunization against diphtheria, tetanus and hepatitis B [24], [25], [26], [27]. Drugs such as penicillin and tetracycline are also related to CPAN, minocyclin being the main one involved. In these cases, withdrawal of medication tends to be followed by improvement of the skin lesions [28], [29], [30].

Until present time, and to our knowledge, there are no studies concerning epidemiological data of CPAN in Brazil, making available in the literature only anecdotal case reports. Hence, our study aims to establish a database on epidemiological, clinical and laboratory information of CPAN patients admitted to the vasculitis clinics of our tertiary hospital.