Systemic Polyarteritis Nodosa Research Articles

Tuberculosis among children and adolescents with rheumatic diseases - case series

Background: Rheumatic patients have a higher frequency of tuberculosis(TB) than the general population. This study aimed to describe children and adolescents with TB and rheumatic diseases(RD) who were being treated in a reference center. Methods: A series of TB cases were investigated in a reference center for childhood TB in Rio de Janeiro, Brazil, from 1995 to 2022. Results: Fifteen patients with underlying RD and TB were included with 8(53%) being female. The mean age at RD diagnosis was 7.10years (SD ± 0,57 years), and the mean age at TB diagnosis was 9.81 years(SD ± 0.88 years). A total of 9 cases of pulmonary TB(PTB) and 6 cases of extrapulmonary TB—pleural(2), joint/osteoarticular(1), cutaneous(1), ocular(1), and peritoneal(1)- were described. The RD observed in the 15 patients included juvenile idiopathic arthritis(9), juvenile systemic lupus erythematosus(3), juvenile dermatomyositis(1), polyarteritis nodosa(1), and pyoderma gangrenosum(1). Among the immunosuppressants/immunobiologics, methotrexate(8) was the most commonly used, followed by corticosteroids(6), etanercept(2), mycophenolate mofetil(1), cyclosporine A(1), adalimumab(1), and tocilizumab(1). The most common symptoms were fever and weight loss, and a predominance of PTB cases was noted. GeneXpert MTB/RIF® was performed in six patients and was detectable in two without rifampicin resistance; Xpert Ultra® was performed in five patients, and traces with indeterminate rifampicin resistance were detected in three. One female patient discontinued treatment, and another passed away. Conclusions: The case series demonstrated the importance of suspecting and investigating TB in RD affected patients who are using immunosuppressants/ immunobiologics, particularly in countries with high rates of TB such as Brazil.

Clinical features and long-term outcomes of patients with systemic polyarteritis nodosa diagnosed since 2005: Data from 196 patients

BackgroundThe landscape of polyarteritis nodosa (PAN) has substantially changed during the last decades. Recent data regarding causes, characteristics, and prognosis of systemic PAN in the modern era are lacking. MethodsThis retrospective study included patients with systemic PAN referred to the French Vasculitis Study Group between 2005 and 2019. Characteristics, associated conditions and outcomes were collected, and predictors of relapse and death were analyzed. Results196 patients were included. Main clinical symptoms were constitutional (84%), neurological (59%), skin (58%) and musculoskeletal (58%) manifestations. Secondary PAN accounted for 55 (28%) patients, including myelodysplastic syndrome (9%), solid cancer (7%), lymphoma (4%) and autoinflammatory diseases (4%). No patient had active HBV infection. All treated patients (98.5%) received glucocorticoids (GCs), alone (41%) or in combination with immunosuppressants (59%), with remission achieved in 90%. Relapses were independently associated with age >65 years (HR 1.85; 95% CI1.12–3.08), gastrointestinal involvement (1.95; 95% CI1.09–3.52) and skin necrotic lesions (HR 1.95; 95%CI 1.24–3.05). One-, 5- and 10-year overall survival rates were 93%, 87% and 81%, respectively. In multivariate analyses, age >65 years (HR 2.80; 95%CI 1.23–6.37), necrotic purpura (HR 4.16; 95%CI 1.62–10.70), acute kidney injury (HR 4.89; 95% 1.71–13.99) and secondary PAN (HR 2.98; 95%CI 1.29–6.85) were independently associated with mortality. ConclusionLandscape of PAN has changed during the last decades, with the disappearance of HBV-PAN and the emergence of secondary PAN. Relapse rate remains high, especially in aged patients with gastrointestinal and cutaneous necrosis, as well as mortality.

Cutaneous arteritis: Clinicopathological study of 21 cases

AbstractObjectivesWe conducted this study to clarify the progress of cutaneous arteritis.MethodsWe examined 21 cases of cutaneous arteritis that were diagnosed at our hospital between 2005 and 2020. The male‐to‐female ratio was 1:6 with a mean age of 52.2 years.ResultsThe lower legs were involved in all cases, and the upper extremities or trunk was also involved in some cases. Cutaneous manifestations presented as indurated erythema (n = 15), subcutaneous induration (11), edema (7), livedo (6), and ulcer (3). In addition, extracutaneous conditions including numbness (10), arthritis (8), fever (2), and myalgia (1) were observed. Laboratory tests showed an increase of inflammatory markers in most cases (14). Histopathological features showed necrotizing vasculitis of small‐sized arteries at the dermo‐subcutaneous junction, and the inflammatory stages of arteritis were histopathologically divided into acute stage (5), subacute stage (5), reparative stage (7), and healed stage (1). The therapies administered were oral prednisolone (11), antiplatelet drug (14), warfarin (1), non‐steroidal anti‐inflammatory drugs (6), biological drug (1), and other drugs (14). There were no cases showing progression to systemic polyarteritis nodosa during follow‐up period. All three patients with ulceration complained of numbness, and one was revealed to have mononeuropathy multiplex. They were treated with low‐dose oral prednisolone. Three ulceration cases were histopathologically classified into the acute and subacute stages.ConclusionsIn conclusion, all 21 patients followed a chronic course with recurrent skin lesions without systemic complications. Cases with ulceration seem to reveal neurological symptoms and need systemic steroid treatment.

Spontaneous Coronary Artery Dissection; A Literature Review

Spontaneous coronary artery dissection (SCAD) is the spontaneous splitting of the coronary tunica media with the formation of a false lumen in the vessel wall and compression of the true lumen. Its incidence is often underestimated, especially in cases of sudden cardiac death before coronary angiography. Predisposing factors include pregnancy, systemic arteriopathy (such as fibromuscular dysplasia), systemic inflammatory conditions ( such as systemic lupus erythematosus and polyarteritis nodosa), systemic connective tissue diseases ( such as Marfan and Ehlers-Danlos syndromes), hypertension and migraine. Common triggering factors involve straining, stress, and hormonal treatment. SCAD is usually diagnosed through coronary angiography, with CT coronary angiography as a non-invasive diagnostic tool. Experts advise minimal coronary instrumentation due to vessel fragility and the risk of dissection extension and vessel occlusion. SCAD patients can have percutaneous coronary intervention (PCI) if they have ongoing ischemia or hemodynamic instability. Coronary artery bypass grafting (CABG) can be an option in cases of failed PCI and high-risk anatomy.

Complications and causes of mortality in patients with primary necrotizing systemic vasculitis

The article reviews the clinical symptoms, main complications in patients with ANCA-associated systemic vasculitis (granulomatous with polyangiitis, microscopic polyangiitis, eosinophilic granulomatous with polyangiitis) and polyarteritis nodosa during the first three years of the disease. We evaluated the relationship between complications and long-term glucocorticosteroid therapy. Patients with granulomatosis had the most unfavourable course of the disease with a high risk of complications. A high incidence of ischemic strokes and chronic kidney disease in patients with microscopic polyangiitis has been identified. We also analyzed cases of lethal outcomes in patients with primary systemic vasculitis.

Clinical features and outcomes of childhood polyarteritis nodosa: A single referral center experience

Objectives The aims of this study were to describe the clinical features, comorbidities and outcome of systemic childhood polyarteritis nodosa (PAN) and to evaluate PAN-like diseases in differential diagnosis. Methods The study group consisted of patients who were diagnosed as PAN in a referral center in Turkey. The files of all patients were reviewed retrospectively. Disease activity was evaluated with pediatric vasculitis activity score (PVAS). Results A total of 19 (13 boys/six girls) patients were enrolled in the study. The mean age of patients was 10.37 ± 3.6 years. The mean duration of follow-up was 5.73 ± 3.74 years. Eight patients (42.1%) were also diagnosed with familial Mediterranean fever (FMF). The cutaneous involvement was higher in patients with PAN than those with FMF-associated PAN (p = .03). The median (min–max) PVAS at diagnosis was 5 (3–7). There was no correlation between PVAS scores at the time of diagnosis and age, clinical findings and relapse. CECR1 mutation was detected in one patient leading to deficiency of adenosine deaminase 2. Conclusion The clinical presentation is variable in children with PAN. PAN-like diseases characterized by necrotizing vasculitis should be considered. The possibility of FMF should be kept in mind if inflammation cannot be controlled.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa.

To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa.

To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

Polyarteritis Nodosa: A Systematic Review of Test Accuracy and Benefits and Harms of Common Treatments.

ObjectiveThe object of this study was to analyze the benefits and harms of different treatment options and to analyze test accuracy used in the evaluation of patients with primary systemic polyarteritis nodosa (PAN).MethodsA systematic search of published English‐language literature was performed in Ovid Medline, PubMed, Embase, and the Cochrane Library from the inception of each database through August 2019. Articles were screened for suitability in addressing patient, intervention, comparison, and outcome questions, with studies presenting the highest level of evidence given preference.ResultsOf 137 articles selected for data abstraction, we analyzed 21 observational studies and seven randomized controlled trials (RCTs). The results showed indirect evidence that a deep skin biopsy provides good diagnostic accuracy. A combined nerve and muscle biopsy should be obtained for patients with PAN with peripheral neuropathy. Cyclophosphamide with high‐dose glucocorticoids (GCs) is effective as an induction treatment for newly diagnosed active and severe PAN. GC monotherapy is adequate in the majority of patients with nonsevere PAN, although it has a high relapse rate with GC taper. There was insufficient data in determining the optimal duration of non‐GC and GC maintenance therapy. Tumor necrosis factor inhibitors are effective treatment for patients with deficiency of adenosine deaminase 2 (DADA2) with stroke and vasculitis manifestations.ConclusionThis comprehensive systematic review synthesizes and evaluates the harms and benefits of different treatment options and the accuracy of commonly used tests for the diagnosis of systemic PAN. Data for diagnosis and management of PAN and DADA2 are mostly limited to observational studies. More high‐quality RCTs are needed.

Overlap between systemic sclerosis and polyarteritis nodosa: A case report

BackgroundSystemic sclerosis (SSc) is a multiorgan connective tissue disease characterized by vasculopathy, inflammation, autoimmunity, and fibrosis in the skin, lungs and other organs. The occurrence of frank vasculitis is uncommon. Case presentationA 36-year old male patient with limited cutaneous SSc developed multiple necrotic ulcers on both legs and feet and gangrene of several toes, followed by an acute onset of axonal sensorimotor neuropathy affecting both radial and peroneal nerves, severe testicular pain with gangrenous patches over the scrotum. The hepatitis B virus (HBV) core antibody was positive while HB surface antigen and surface antibody, HAV and HCV antibodies were negative. The polymerase chain reaction for HBV and HCV showed no detectable viraemia. Antineutrophil cytoplasmic antibodies, cryoblobulins, anticardiolipin antibodies, lupus anticoagulant, antimitochondrial and anti- liver-kidney microsomal antibodies were negative. Pelvi-abdominal ultrasound and portal vein Doppler study showed a coarse and heterogeneous echo-texture of the liver, splenomegaly, moderate ascites and an enlarged, patent portal vein. Fibroscan revealed grade III liver fibrosis. He had an attack of haematemesis with elevation of the liver enzymes and low serum albumin and prothrombin concentrations. He was diagnosed as a case of polyarteritis nodosa. He was successfully treated by methylprednisolone intravenous pulses, followed by oral prednisone 40 mg/day. Plasmapheresis and six monthly doses of 1000 mg intravenous cyclophosphamide. Prednisone was gradually tapered to 5 mg/day with addition of azathioprine 100 mg/day. ConclusionThe association between systemic sclerosis and polyarteritis nodosa is very rare. The co-existence of SSc and vasculitis necessitates modification of the treatment plan.

Survey of Japanese dermatological vasculitis specialists on cases of cutaneous arteritis (cutaneous polyarteritis nodosa).

We developed a questionnaire to examine the findings of cutaneous arteritis among dermatological specialists experienced in vasculitis as certified by the Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. We sent a questionnaire to 12 dermatological facilities identified through the revised Committee for guidelines for the management of vasculitis and vascular disorders of the Japanese Dermatological Association. Retrospective data obtained from 84 patients at the 12 dermatological facilities between 2012 January 2016 December were evaluated. The 84 patients were categorized into two groups, a systemic steroid treatment group (group 1, n=52) and a no systemic steroid treatment group (group 2, n=32). C-reactive protein in group 1 patients was significantly higher than that in group 2 patients. Frequency of fever, arthritis, myalgia- and peripheral neuropathy in group 1 was significantly higher than that in group 2. We propose that these symptoms could serve as early markers for the transfer from cutaneous arteritis to systemic polyarteritis nodosa. We further suggest that patients who are subsequently associated with cerebral hemorrhage and infarction, who are originally diagnosed as having cutaneous arteritis, could progress to systemic polyarteritis nodosa. The study demonstrated that it is important for dermatologists to detect these findings early in order to establish an accurate diagnosis and a timely treatment.

Analysis of the Clinical Characteristics and Follow-up Study of Children with Cutaneous Polyarteritis Nodosa.

This study aims to analyze the clinical characteristics, treatment and prognosis of children with cutaneous polyarteritis nodosa (CPAN), in order to improve the understanding of this disease. Data of 14 children with CPAN, who were hospitalized in the Beijing Children's Hospital of Capital Medical University from January 2006 to December 2016, were collected. The clinical characteristics of all patients were summarized, the antistreptolysin-O (ASO)-positive and ASO-negative groups were compared, and the follow-up results were analyzed. X2-test, Fisher's exact probability test, t-test and Mann-Whitney test were used for statistical analysis. Among these 14 CPAN patients, nodular rash was the most common manifestation (14/14). The ASO-positive group had more nodules in the lower limbs and the ASO-negative group appeared more in the upper limbs, which were statistically significant (p<0.05). ASOpositive children were more likely to have joint symptoms (P<0.05), and were more prone to elevated white blood cells (P<0.05). Follow-ups were performed on nine patients, and the prognoses were all good. The occurrence of systemic polyarteritis nodosa was not observed. The main clinical manifestation of children with CPAN is skin nodules, which rarely affects the internal organs. Streptococcal infection is often the main cause. Anti-infection treatment should be simultaneously considered.

Cutaneous alterations in vasculitides : Part2: Special aspects of diseases of large, medium and small vessels

Cutaneous vasculitides present with typical clinical signs depending on the size and distribution of the affected vessels. Since there are no large vessels in the skin, giant cell arteritis and Takayasu's arteritis only rarely lead to cutaneous symptoms. The classical systemic polyarteritis nodosa (PAN) is very rare. More frequent is cutaneous PAN presenting with atypical localized livedo racemosa and palpable subcutaneous nodules. The ANCA-associated vasculitides, which belong to the small vessel vasculitides, usually show systemic involvement and manifest on the skin with adiverse picture. Immune complex vasculitides are characterized by deposition of immunoglobulins on the walls of small vessels. The most common form is IgA vasculitis with the cardinal symptoms of palpable, round or oval and partially branched (retiform) purpura and a clear predilection for the legs. Serum disease is apríme example of systemic immune complex diseases due to large circulating immune complexes. Cryoglobulinemic vasculitis primarily involves small as well as medium sized vessels. Simultaneous involvement of vessels of different sizes is characteristic for vasculitis in systemic lupus erythematosus (SLE), Sjögren's syndrome, rheumatoid arthritis and sarcoidosis. Recurrent macular vasculitis in hypergammaglobulinemia is an episodic macular vasculitis of the small blood vessels. Bacteremic vasculitis of the small vessels (without direct microbial infection of the vessel wall) can typically also affect capillaries of dermal papillae and is usually accompanied by adisseminated intravascular coagulation (DIC). In some cases more than one distinct cutaneous vasculitis can occur in the same patient.

Recurrent ruptured abdominal aneurysms in polyarteritis nodosa successfully treated with infliximab.

Systemic polyarteritis nodosa (PAN) is a rare form of necrotizing vasculitis in children. Recurrent episodes of abdominal aneurysm ruptures are uncommon and life-threatening condition in children. Failures of response to immunosuppressive medications and radiological intervention also lead to high mortality. Some reports suggested that tumor necrosis factor (TNF) might have role in the inflammation of this disease. After an English-language literature review, this is the first case report in children of recurrent abdominal-ruptured aneurysms with a failure of conventional therapy but successfully treated with anti-TNF-α monoclonal antibody. We herein describe a 9-year-old girl who presented with chronic abdominal pain, hypertension, and massive lower gastrointestinal bleeding. The disease was refractory to conventional treatment, including administration of a corticosteroid, cyclophosphamide, and intravenous immunoglobulin, and recurrent-ruptured aneurysms developed in the gastrointestinal tract. Arterial embolization during angiography resulted in temporary improvement of the gastrointestinal bleeding. Infliximab, a chimeric anti-tumor necrosis factor-α monoclonal antibody, was initiated and resulted in disease remission with resolution of the gastrointestinal bleeding and abdominal pain. Anti-TNF therapy might be another treatment option for refractory disease to prevent ongoing inflammation that could lead to aneurysmal dilatation or even rupture. However, early recognition of refractory disease and aggressive treatment in the early course of the disease are crucial to reduce morbidity and mortality.

Poliarteritis nodosa sistémica y cutánea en niños

La Poliarteritis Nodosa (PAN) se define como la arteritis necrotizante de arterias de mediano y pequeño calibre, sin glomerulonefritis o vasculitis en arteriolas, capilares o vénulas, y sin asociación a anticuerpos anticitoplasma de neutrófilos (ANCA). La PAN es más frecuente en adultos, con igual presentación en ambos sexos. Se presenta el caso de un niño de 13 años de edad, con fiebre prolongada, artralgias, miositis, edema de miembros inferiores, lesiones petequiales y equimóticas generalizadas, trombosis venosa profunda en pierna izquierda, isquemia con posterior necrosis del dedo pulgar izquierdo, con diagnóstico de PAN sistémica; recibió tratamiento con corticoides, IGIV y ciclofosfamida, con mejoría clínica y posterior alta. El segundo caso corresponde a un varón de 9 años de edad, con cuadro de fiebre, dolor abdominal, náuseas, vómitos, nódulos palpables y petequias en miembros inferiores y superiores, livedo reticularis en miembros inferiores, artritis en tobillos, con diagnóstico de PANc, habiendo recibido solamente corticoides, con excelente evolución.

Causal relationship between acute pancreatitis and methylprednisolone pulse therapy for fulminant autoimmune hepatitis: a case report and review of literature

BackgroundA causal relationship between acute pancreatitis and administration of glucocorticoids remains a matter of debate, since most of the reported cases were diagnosed with systemic vascular diseases (including systemic lupus erythematosus and polyarteritis nodosa) that may be responsible for the pancreatitis.Case presentationWe report a case of a 51-year-old woman who developed acute pancreatitis after receiving methylprednisolone pulse therapy for the treatment of fulminant autoimmune hepatitis (AIH). She was admitted to our hospital because of overt jaundice and back pain. Since her liver dysfunction deteriorated progressively, a liver biopsy was performed and a diagnosis of AIH was established. She was given intravenous methylprednisolone pulse therapy at 1000 mg/day for 3 days, and oral prednisolone at 40 mg/day thereafter. While her liver function improved rapidly, she started complaining of mild back pain and serum amylase and lipase levels were elevated from 5 days after the initiation of steroid therapy. A CT scan revealed mildly edematous changes around the pancreas, leading to a diagnosis of acute pancreatitis. After tapering off prednisolone, back pain disappeared, and elevated serum amylase was normalized without exacerbation of AIH. A systematic literature review identified 8 cases of acute pancreatitis developing after administration of corticosteroid pulse therapy with a median latent period of 5 days.ConclusionsThe present case and reports in the literature suggest that steroid pulse therapy may cause acute pancreatitis in patients having no signs of systemic vasculitis.

Cutaneous polyarteritis nodosa: Diagnosis lies skin deep

Cutaneous polyarteritis nodosa (CPAN) is an uncommon form of cutaneous vasculitis. Definitive diagnosis is based on skin biopsy. We present a rare case of CPAN in a 2-year-old male child who presented with a history of fever, cutaneous ulcers, and digital gangrene. He was treated with steroids and skin lesions had resolved completely. CPAN needs to be differentiated from systemic polyarteritis nodosa for specific prognosis and management. We report this case to highlight the need of early diagnosis for faster recovery with favorable outcome.

Cutaneous Manifestations of Medium- and Large-Vessel Vasculitis.

Dermatologic manifestations are observed in almost all systemic vasculitides, even in large-and medium-vessel vasculitides, although such vessels are not found in the skin. Cutaneous manifestations may be related to a direct skin localization of the systemic vasculitis or a non-specific process associated with the vasculitis. According to the 2012 International Chapel Hill consensus, the two major variants of large-vessel vasculitides are Takayasu arteritis and giant-cell arteritis. In Europe and North America, acute inflammatory nodules or erythema nodosum-like lesions are the most commonly observed skin lesions with Takayasu arteritis. Medium-sized arteriole vasculitis of the dermis or subcutis but also septal or lobular panniculitis may be found during pathological examination. In Japan, widespread pyoderma gangrenosum-like lesions are more frequent. Cutaneous manifestations of giant-cell arteritis are rare; they are ischemic, linked to arterial occlusions, or non-ischemic, with various mechanisms. The two major medium-vessel vasculitides are Kawasaki disease and polyarteritis nodosa. Kawasaki disease is characterized by a mucocutaneous lymph node syndrome without skin vasculitis. Two subsets of polyarteritis nodosa with different skin manifestations are described, without transition from one to the other. In the systemic subset, the most frequent skin lesions are in the order of frequency purpura, livedo, and nodules. Cutaneous polyarteritis nodosa mainly features nodules, livedo racemosa, and ulcerations. Genetic screening and measurement of plasma levels of adenosine deaminase 2 should be considered for patients with uncommon systemic polyarteritis nodosa or early-onset cutaneous polyarteritis nodosa.

Monogenic polyarteritis: the lesson of ADA2 deficiency

The deficiency of Adenosine Deaminase 2 (DADA2) is a new autoinflammatory disease characterised by an early onset vasculopathy with livedoid skin rash associated with systemic manifestations, CNS involvement and mild immunodeficiency.This condition is secondary to autosomal recessive mutations of CECR1 (Cat Eye Syndrome Chromosome Region 1) gene, mapped to chromosome 22q11.1, that encodes for the enzymatic protein adenosine deaminase 2 (ADA2). By now 19 different mutations in CECR1 gene have been detected.The pathogenetic mechanism of DADA2 is still unclear. ADA2 in a secreted protein mainly expressed by cells of the myeloid lineage; its enzymatic activity is higher in conditions of hypoxia, inflammation and oncogenesis. Moreover ADA2 is able to induce macrophages proliferation and differentiation; it’s deficiency is in fact associated with a reduction of anti-inflammatory macrophages (M2). The deficiency of ADA2 is also associated with an up-regulation of neutrophils-expressed genes and an increased secretion of pro-inflammatory cytokines. The mild immunodeficiency detected in many DADA2 patients suggests a role of this protein in the adaptive immune response; an increased mortality of B cells and a reduction in the number of memory B cells, terminally differentiated B cells and plasmacells has been described in many patients. The lack of the protein is associated with endothelium damage; however the function of this protein in the endothelial homeostasis is still unknown.From the clinical point of view, this disease is characterized by a wide spectrum of severity. Chronic or recurrent systemic inflammation with fever, elevation of acute phase reactants and skin manifestations (mainly represented by livedo reticularis) is the typical clinical picture. While in some patients the disease is mild and skin-limited, others present a severe, even lethal, disease with multi-organ involvement; the CNS involvement is rather common with ischemic or hemorrhagic strokes. In many patients not only the clinical picture but also the histopathologic features are undistinguishable from those of systemic polyarteritis nodosa (PAN). Of note, patients with an unusual phenotype, mainly dominated by clinical manifestations suggestive for an immune-disrective condition, have been described.Due to its rarity, the response to treatment of DADA2 is still anecdotal. While steroids can control the disease’s manifestations at high dosage, none of the common immunosuppressive drugs turned out to be effective. Biologic drugs have been used only in few patients, without a clear effectiveness; anti-TNF drugs are those associated to a better clinical response. Hematopoietic stem cells transplantation was effective in patients with a severe phenotype.

Kaleidoscope of autoimmune diseases in HIV infection.

Within the last 30years, the human immunodeficiency virus (HIV) infection has changed its status from inevitably fatal to chronic disorder with limited impact on life span. However, this breakthrough was mainly the effect of introduction of the aggressive antiviral treatment, which has led to the clinically significant increase in CD4+ cell count, resulting in fewer cases of the acquired immunodeficiency syndrome (AIDS) and improved management of opportunistic infections occurring in the course of the disease. The occurrence of a particular autoimmune disease depends on degree of immunosuppression of the HIV-positive patient. In 2002, four stages of autoimmunity were proposed in patients infected by HIV, based on the absolute CD4+ cell count, feature of AIDS as well as on the presence of autoimmune diseases. Spectrum of autoimmune diseases associated with HIV infection seems to be unexpectedly wide, involving several organs, such as lungs (sarcoidosis), thyroid gland (Graves' disease), liver (autoimmune hepatitis), connective tissue (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa and other types of vasculitis, antiphospholipid syndrome) or hematopoietic system (autoimmune cytopenias). This paper contains the state of art on possible coincidences between HIV infection and a differential types of autoimmune diseases, including the potential mechanisms of this phenomenon. As the clinical manifestations of autoimmunization often mimic those inscribed in the course of HIV infection, health care providers should be aware of this rare but potentially deadly association and actively seek for its symptoms in their patients.