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Objectives: Infections remain a major cause of morbidity and mortality in systemic necrotizing vasculitides (SNV). We aimed to identify factors predicting severe infections (SI) in SNV., Methods: Data from five randomized controlled trials (RCTs) enrolling 733 patients were pooled. The primary end point was the occurrence of SI, defined by the need of a hospitalization and/or intravenous anti-infectious treatment and/or leading to death., Results: After a median follow-up of 5.2 (interquartile range 3-9.7) years, 148 (20.2%) patients experienced 189 SI, and 98 (66.2%) presented their first SI within the first 2 years. Median interval from inclusion to SI was 14.9 (4.3-51.7) months. Age ≥65 years (hazard ratio (HR) 1.49 [1.07-2.07]; P=0.019), pulmonary involvement (HR 1.82 [1.26-2.62]; P=0.001) and Five Factor Score ≥1 (HR 1.21 [1.03-1.43]; P=0.019) were independent predictive factors of SI. Regarding induction therapy, the occurrence of SI was associated with the combination of GCs and CYC (HR 1.51 [1.03-2.22]; P = 0.036), while patients receiving only GCs were less likely to present SI (HR 0.69 [0.44-1.07]; P = 0.096). Finally, occurrence of SI had a significant negative impact on survival (P<0.001)., Conclusion: SI in SNV are frequent and impact mortality. Age, pulmonary involvement and Five Factor Score are baseline independent predictors of SI. No therapeutic regimen was significantly associated with SI but patients receiving glucocorticoids and CYC as induction tended to have more SI., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We report a case of cerebral vasculitis in a 31-year-old woman who presented with chronic kidney disease stage 5, labile hypertension and severe headaches. The diagnosis of cerebral vasculitis made on magnetic resonance angiography (MRA) and late diagnosis of polyarteritis nodosa were made by conventional CT angiography. Immunosuppression was complicated by recurrent septicaemia due to Elizabethkingia meningoseptica Treatment of the vasculitis resulted in marked improvement of MRA appearances, headaches and anxiety and stabilisation of blood pressure. The septicaemia required parenteral quinolone treatment and oral cotrimoxazole., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Case of 59-year-old male with chronic obstructive pulmonary disease and a number of comorbidities, who has developed meningoencephalitis caused by Cryptococcus neoformans var. grubii with polyarteritis nodosa diagnosed during hospitalization, was presented. Before evidence of meningoencephalitis, the patient was being treated with ketoconazole and low doses of fluconazole (200 mg/day) for alleged candidiasis. The dosage was increased (800 mg/day) following laboratory diagnosis of C. neoformans based on positive latex agglutination test and biochemical identification of encapsulated yeast isolated from the blood and CSF. Later, the yeast identification was confirmed by sequencing analysis. Owing to inadequate clinical response, fluconazole therapy was switched to voriconazole (400 mg/day) and later to intravenous amphotericin B (1.0 mg/kg per day). Despite of a temporary stabilization and improvement, which correlated with decline of cryptococcal antigen titers (from 1:1024 to 1:8), after 6 weeks, the patient's underlying condition deteriorated due to severe pancolitis and serious nosocomial bacterial infections. The patient died of multiorgan failure several days later. Our case demonstrates a possible connection between the development of life-threatening cryptococcosis and an autoimmune vasculitis disease and emphasizes that the outcome of the management of cryptococcal meningoencephalitis is highly dependent on early diagnosis, adequate treatment, including dosage, and last but not least control of underlying disease and risk factors.

Purpose of Review: Microbial factors are supposed to play an inducing and/or reactivating role in many of the idiopathic systemic vasculitides. This review evaluates the evidence that microbes are involved in the etiopathogenesis of the disease focusing on possibilities for antimicrobial intervention., Recent Findings: The clinical presentation of hepatitis B virus (HBV)-associated polyarteritis nodosa (PAN) is different from that of non-HBV-PAN and requires antiviral treatment. In hepatitic C virus (HCV)-associated autoimmune diseases, type 2 cryoglobulinemia is present in 52% of cases. Chronic nasal carriage of Staphylococcus aureus is related to endonasal activity of Wegener's granulomatosis and recurrent relapses, and prophylactic treatment with co-trimoxazole is effective in reducing relapse rate., Summary: Patients with PAN should be tested for HBV, and patients with type 2 cryoglobulinemia for HCV. When tested positive, antiviral treatment should be considered. Patients with Wegener's granulomatosis should be tested for nasal carriage of S. aureus, and prophylactic treatment with co-trimoxazole should be considered in case of persistent endonasal activity of Wegener's granulomatosis together with S. aureus carriage. The efficacy of S. aureus elimination for preventing relapses of Wegener's granulomatosis should be evaluated.

Polyarteritis nodosa is a rare vasculitis of small and medium arteries. It can occur in a systemic form with multi-organ involvement, or as a limited form confined to the skin, muscles, joints and peripheral nerves called cutaneous polyarteritis nodosa. Both forms are rare in adults and even more in children. The caues of this vasculitis remain unknown but some viruses and bacteria have been implicated, specially, Streptococcus. We present the case of a 6-year-old child who developed cutaneous polyarteritis nodosa following a probable streptococcal infection.

Mycobacterium fortuitum is a rapidly growing mycobacterium found in soil and water throughout the world. It can cause diseases in immunocompetent patients, usually resulting in localized skin and soft tissue infections. Cervical lymphadenitis caused by M. fortuitum is rare. We report a 46-year-old woman in whom skin lesions of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and Sweet's syndrome had successively developed before the diagnosis of cervical lymphadenitis caused by M. fortuitum was made. The skin lesions responded to colchicine and systemic corticosteroids but recurred intermittently. After establishment of the diagnosis, she received treatment with clarithromycin and ciprofloxacin. The cervical lymph nodes decreased in size 6 months later and no more new skin lesions were found.

We report a case of adult polyarteritis nodosa (PN) associated with group A streptococcal infection. A 37-year-old male had suffered from high fever, polyarthralgia, myalgia, and exanthema following pharyngalgia. He was admitted to the hospital because of cutaneous ulcers and necrosis making the general condition rapidly poor. A serological streptococcal test showed a marked increase in antistreptlysin-O (ASO) and a positive reaction to C polysaccharide, suggesting fulminant streptococcal infection. Various antibiotics including penicillin agents were administered. However improvement and exacerbation were repeatedly noted. In the hospital course peripheral neuritis and subcutaneous nodes in upper extremities developed. Biopsy specimen of subcutaneous nodes revealed necrotizing angiitis. Administration of a steroid achieved complete response, and the symptoms, inflammatory reaction, and ASO level improved. While the dose of the steroid was tapered gradually, recurrence was noted. However, increasing the dose finally resulted in relief. During the 2-year follow-up, there was a correlation between the ASO level and inflammatory reaction.

Polyarteritis nodosa (PAN) is a necrotizing arteritis of small and medium-sized vessels. It may present with hypertension and/or renal insufficiency. Peripheral neuropathy, myopathy, joint pains, testicular pain, and ischemic myalgias may also be seen. Gastrointestinal involvement may lead to gangrene of the bowel, peritonitis, perforation, intra-abdominal hemorrhage, and pancreatitis. The cutaneous manifestations include tender subcutaneous nodules grouped along the course of superficial arteries of the lower extremities, with or without an overlying livedo reticularis. Although multisystem involvement is characteristic, sometimes only one organ or system may be involved. Associations with viral hepatitis (both B and C) and streptococcal infection have been established for PAN. Recurrent strep infections of the upper respiratory tract, streptococcal glomerulonephritis and rheumatic fever have previously been linked to PAN. This report extends the spectrum of associated streptococcal infections to include necrotizing fasciitis.

We report a young girl who developed ingravescent intestinal symptoms as the first manifestation of cutaneous polyarteritis nodosa (PAN) while the typical skin nodules developed later during the disease course. Cutaneous PAN predominantly affects children and presents with crops of painful skin nodules in the medial aspect of the foot, often preceded by sore throat. Visceral manifestations including gut involvement are commonly associated with the classical form of PAN while they are rarely reported in the cutaneous form. In our patient the severity of the abdominal symptoms required a laparoscopy, which revealed diffuse erythematosus swelling of the intestine on the serosal side. The administration of penicillin and steroids was followed by a dramatic improvement in the disease course. Chronic anterior uveitis developed 4 months after the disease onset and responded to local treatment. At a 2-year follow-up the girl is in good condition under prophylaxis with benzathine-penicillin with no recurrence of the illness. Our case confirms that cutaneous PAN is often related to streptococcal infection, and suggests that ASO titers should be determined in children with vasculitides to ensure a timely diagnosis and treatment of the condition if present.

Objective: To test the hypothesis that some cases of primary vasculitis are caused by ehrlichiosis., Design: A retrospective case study and serological analysis of stored sera., Setting: University hospital., Subjects: Fifty-five patients discharged with any type of vasculitis over a 6-year period., Main Outcome Measures: Serology for human monocytic ehrlichiosis, and the human granulocytic ehrlichiosis agent, and polymerase chain reaction (PCR) analysis of biopsy specimens., Results: Three patients (5.5%) had titres of 1 : 128 or higher against E. chaffeensis; none was positive for the human granulocytic ehrlichiosis agent. Skin biopsies of these patients showed lesions compatible with polyarteritis nodosa, allergic purpura and unspecified vasculitis. PCR analysis of the biopsies was unrevealing., Conclusions: Infection with human monocytic ehrlichiosis may underlie some forms of vasculitis. If confirmed, these findings may help identify patients with vasculitis who would benefit from antibiotic treatment.

Classic polyarteritis nodosa is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries. In most cases, the causes of polyarteritis nodosa remain unknown, but viruses (HBV, HCV, HIV) and microbes (especially streptococcus) have been considered as etiologic or contributing factors. A 13-year-old boy was admitted with fever, skin lesions, polyarthritis and muscle involvement. A muscle biopsy demonstrated a necrotizing vasculitis and antistreptolysin titre was tremendously increased. His condition improved following the administration of oral steroids but he experienced relapses 5 and 12 years later when penicillin withdrawal was attempted. The flares were accompanied by a major increase of antistreptolysin titre and response to corticosteroid was obtained. He is currently 38 years old and he remains well on prophylactic penicillin. Polyarteritis nodosa in children may occur after a streptococcal infection. It may be prudent to consider penicillin prophylaxis in patients with periarteritis nodosa when a streptococcal etiology is documented or highly suspected.

Objective: Pneumonia due to Pneumocystis carinii has been increasingly reported in patients with connective tissue diseases, but the frequency of this complication is not known. We sought to determine the frequency of P carinii pneumonia (PCP) in patients with connective tissue diseases, and to determine the role that a hospital's acquired immunodeficiency syndrome (AIDS)-related experience may have in the diagnosis of PCP in these patients., Methods: We used a state hospitalization registry to identify all patients with PCP and either rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, polymyositis, dermatomyositis, polyarteritis nodosa, or scleroderma who had an emergent or urgent hospitalization in California from 1983 to 1994. We compared patient and hospital characteristics between these patients and patients with connective tissue diseases hospitalized with other types of pneumonia., Results: Two hundred twenty-three patients with connective tissue diseases were diagnosed with PCP in the 12-year study period. The frequency of PCP ranged from 89 cases/10,000 hospitalizations/year in patients with Wegener's granulomatosis to 2 cases/10,000 hospitalizations/year in patients with rheumatoid arthritis. Compared with 5,457 patients with connective tissue diseases and pneumonia due to other organisms, patients with PCP were more likely to be younger, to be male, to have private medical insurance, and to have systemic lupus erythematosus, Wegener's granulomatosis, inflammatory myopathy, or polyarteritis nodosa rather than rheumatoid arthritis, and were less likely to be African American. Hospital size, teaching status, urban/rural location, proportion of admissions due to AIDS or PCP, and proportion of patients with pneumonia undergoing bronchoscopy were each associated with the likelihood of diagnosis of PCP in univariate analyses, but only the number of patients with PCP being treated at a hospital (odds ratio [OR] 1.03 for each additional 10 cases/year, 95% confidence interval [95% CI] 1.01-1.05) was associated with the likelihood of diagnosis of PCP in multivariate analyses. Patients were also somewhat more likely to be diagnosed with PCP if there had previously been a case of PCP in a patient with a connective tissue disease at the same hospital (OR 135, 95% CI 0.98-1.85). In-hospital mortality was 45.7%, and was unrelated to hospital characteristics., Conclusion: PCP is an uncommon, but often fatal, occurrence in patients with connective tissue disease. A hospital's prior experience with patients with PCP is associated with the likelihood that this condition is diagnosed in patients with connective tissue diseases who present with pneumonia, suggesting that diagnostic suspicion is an important factor in the correct identification of affected patients.

Background: Polyarteritis nodosa is an aggressive, often fatal form of vasculitis associated with multi-organ involvement. Cutaneous polyarteritis nodosa is purported to be a more benign form of this disorder with involvement limited to the skin., Methods: The identification of a female patient from childhood to adulthood documenting repeated episodes of cutaneous polyarteritis nodosa following bouts of recurrent streptococcal pharyngitis., Results: Repeated bouts of streptococcal pharyngitis at ages 11, 28, and 33 years were followed by episodes of cutaneous polyarteritis nodosa, documented by histopathologic skin changes and clinical presentation, and confirmed by therapeutic management., Conclusions: Various infectious and non-infectious conditions have been linked both to the initiation and relapse of this disease. We describe a patient with recurrent episodes of cutaneous polyarteritis nodosa spanning a period of over 20 years with each episode appearing to be linked to a prior streptococcal infection.

Polyarteritis nodosa (PAN) is a multisystem inflammatory disease associated with necrotizing vasculitis of small and medium arteries. Although predominantly an adult disease, PAN is well described in children. It can occur in a systemic form with manifestations in skin, joints, heart, nervous system, gastrointestinal tract, lungs and kidneys, and a limited form in which disease is confined to the skin, muscles, joints and peripheral nerves. In either case, streptococcal infection has been implicated by a positive throat swab or a significant increase in either antistreptolysin O (ASOT) or antihyaluronidase titres. The limited form is thought to run a benign course, but little has been written about its long-term outcome. We describe two patients who developed a cutaneous vasculitis following a probable streptococcal infection. Both have run a relapsing and remitting course with significant elevations of ASOT and in one, at least, prophylactic penicillin has had a strikingly beneficial effect. In both patients, the disease seems to have receded during childhood, only to recur, retaining its original form, in adult life. Their current ages are 22 and 19 yr, respectively.

A boy with diagnostically unclear vasculitis was described, in which development of the disease points out the presence of cutaneous form of poliarteritis nodosa. Nevertheless, there are also signs for systemic form of the disease. His symptoms are marked cutaneous eruptions of the livedo reticularis type, recidives of erythema nodosum on the limbs and trunk, even on the cheeks, sometimes accompanied with fever, arthralgias, myalgias and cutaneous ulcera on the places of mechanical pressure (elbows), but also with monotopic ventricular premature beats and sporadic microhaematuria. Clinical development of the disease and differential diagnosis exclude other autoimmune disorders with great probability. The positive finding of cANCA has pointed out the diagnosis of vasculitis. Microscopical analysis of the skin didn't reveal any pathological changes. In the boy's disease is interposed a streptococcal infection, and maybe, tuberculosis. The paper deals with wide spectrum of diseases in differential diagnosis, and also with a possible role of bacterial superantigens in the genesis of autoimmunity.

Background: The clinical presentation of childhood polyarteritis nodosa (PAN) can range from isolated cutaneous findings to widespread multisystem involvement. Both the systemic and cutaneous forms are known to occur after streptococcal infection., Objective: Our purpose was to emphasize the frequent association of childhood cutaneous PAN with antecedent streptococcal infection., Methods: We discuss four cases of cutaneous PAN that were associated with streptococcal infection and briefly review the pertinent literature., Results: All patients had evidence of preceding streptococcal infection at the onset of their illness. Although mild systemic symptoms were present in all, their course was benign. The use of nonsteroidal antiinflammatory agents or corticosteroids resulted in clinical improvement. Antibiotic therapy was also used in the treatment of these patients., Conclusion: In children with PAN, evaluation should include laboratory studies to detect streptococcal infection.

We describe three patients who had infection with human parvovirus B19 in association with new-onset systemic necrotising vasculitis syndromes, two with features of polyarteritis nodosa and one with features of Wegener's granulomatosis. Chronic B19 infection, lasting 5 months to more than 3 years, was shown by enzyme immunoassay for IgG and IgM antibodies to B19 and polymerase chain reaction for B19 DNA in serum and tissue samples. The patients had atypical serological responses to the B19 infection, although none had a recognisable immunodeficiency disorder. Treatment with corticosteroids and cyclophosphamide did not control vasculitis. Intravenous immunoglobulin (IVIG) therapy led to rapid improvement of the systemic vascultis manifestations, clearing of the chronic parvovirus infection, and long-term remission. These observations suggest an aetiological relation between parvovirus B19 infection and systemic necrotising vasculitis in these patients and indicate a potentially curative role for IVIG in such disorders.

An adult patient had a syndrome associating the features of juvenile dermatomyositis and cutaneous polyarteritis nodosa that followed a cyclic course from childhood; recurrences were always associated with a rise of serum antistreptococcal antibodies. Regions of homology between streptococcal type 5 M protein and skeletal myosin were found. These findings suggest that streptococcal infection, possibly through a molecular mimicry mechanism, played a role in the pathogenesis of the disease in our patient.

In order to assess the prevalence of hepatitis C virus (HCV) in polyarteritis nodosa (PN), 38 patients with systemic necrotizing angiitis were retrospectively tested for the presence of anti-HCV antibodies (Ab). Twenty-one patients were hepatitis B virus (HBV) positive, comprising group A, and 17 were HBV negative, comprising group B. Two patients from group A had anti-HCV Ab (2/21: 9.5%). One was treated unsuccessfully with corticosteroids, then with vidarabine and plasma exchanges; HBe/anti-HBe seroconversion was not observed and anti-HCV Ab disappeared 8 months after the onset of PN. The second patient was successfully treated with corticosteroids, then vidarabine and plasma exchanges; he recovered from PN, HBV seroconversion occurred, and the anti HCV Ab remained detectable. These results show that: 1) the prevalence of anti HCV Ab in PN related to HBV is nearly the same (9.5%) as the prevalence of HCV Ab observed in patients with chronic hepatitis related to HBV infection; 2) the course of these two viral infections can be different and the role of HCV as an etiologic factor in PN has not been established.

Poststreptococcal reactive arthritis is most likely a form of acute rheumatic fever. However, it frequently differs by early development of arthritis after pharyngitis, more prolonged arthritis or arthralgia and a less dramatic response to aspirin. The use of prophylactic penicillin is discussed and advocated. Childhood polyarteritis may be divided into a cutaneous form and a more generalized form that usually involves the kidney but frequently also the gastrointestinal tract, heart, or nervous system. Nine children with polyarteritis nodosa are described and their disease related to a prior streptococcal infection.

We have investigated hepatitis B virus (HBV) infection in systemic necrotizing vasculitis (SNV). Our approach included the detection of the viral surface antigen (HBsAg) with a radioimmunoassay employing monoclonal anti-HBs (m-RIA); in addition, HBV DNA was looked for in serum and peripheral mononuclear blood cells. Among 28 subjects with SNV, 12 were found to be positive for HBsAg with the conventional test (p-RIA) and 7 additional subjects had anti-HBc and/or anti-HBs. From the 16 HBsAg negative individuals, 9 had HBsAg epitopes identified in serum with the m-RIA test and 1 had a low amount of circulating viral DNA. In contrast, only 1 among 6 subjects with other systemic vasculitis showed a positive test for m-RIA and HBV DNA assays; this individual had acquired HIV infection through transfusions which were also probably the source of his HBV infection. HBV DNA sequences were identified in peripheral mononuclear blood cells of 9 from the 37 tested, including 2 individuals who were HBsAg positive only with m-RIA. Therefore, our study indicates a much higher rate of HBV infection in patients with polyarteritis nodosa than previously suspected.

Testing for e antigen and antibody (anti-e) was performed by immunodiffusion and counterelectrophoresis in patients with polyarteritis nodosa fulminant hepatitis, and chronic active hepatitis (CAH), in 59 asymptomatic carriers of hepatitis B surface antigen (HBsAg) who underwent liver biopsy, and in 150 carriers followed with sequential SGPT determinations. Counterelectrophoresis was more sensitive that immunodiffusion. Neither e antigen nor anti-e was found in the absence of HBsAg. Among HCsAg-positive patients with polyarteritis nodosa and CAH, e antigen was found in 16 of 18 and 13 of 22, respectively. It was not found in any of 43 patients with fulminant hepatitis, of whom 24 were HBsAg-positive. The e antigen was detected in none of 13 biopsied carriers with normal histology, 4 of 28 with nonspecific changes of 11 of 18 with CAH or chronic persistent hepatitis. Conversely, anti-e was present in 9 of 13 with normal biopsy, 7 of 28 with nonspecific changes, and none of 18 with CAH or chronic persistent hepatitis. The e antigen was found more commonly in nonbiopsied carriers with elevated SGPT, and anti-e in those with normal SGPT. Six carriers whose antigenemia terminated spontaneously had anti-e. The presence of e antigen correlated with a high titer of HBsAg, and with immunofluorescent detection of hepatitis B core antigen in the nuclei of hepatocytes. Conversely, anti-e was associated with significantly lower titers of serum HBsAg (P less than 0.001) and lack of detectable hepatitis B core antigen in the liver.

The small vessel's necrotizing angiitis (necrotizing microangiitis (NMA), leucocytoclastic angiitis) form a continuous spectrum from the exclusively cutaneous forms of Gougreot, to those which seriously affect the viscera, as the very acute and fatal cases of Zeek, passing through a series of intermediate phases, in which Schönlein-Henoch's purpura is found. In all of these clinical forms, the existence of an allergic mechanism has been suggested from their origin itself and in 1964 Alarcón-Segovia and Brown grouped them under the common denominator of allergic angiitis. Later investigations are far from completely confirming this hypothesis. In isolated cases, the clinical sequence corroborates the hypothesis of a bacterian aetiology (local septic focus), but in the Schónlein-Henoch purpura it has not been proven that there is a greater streptococcus beta-haemolytic frequency is the throat nor a greater number of antibodies in the serum than in normal children or those affected by illnesses not related to rheumatic fever. The aetiologic role of drugs and food is very difficult to prove. The anatomopathologic similarity between the Arthus reaction, the serum sickness and the spontaneous human NMA have led to the hypothesis that the NMA are immunocomplex (IC) diseases. In order to try to prove this, basically three techniques have been used: Direct immunofluorescence to show the IC tissue deposits, and mixed cryoglobulinemia and the serum's anti-complementary activity for the circulating IC. Direct immunofluorescence shows, in approximately 50% of the cases, the presence of IgG and C3 in the damaged vessels (also IgM with frequency). But, are these found combined as complexes? Parish, in some cases of presumably post-bacterial angiitis, has shown the simultaneous presence of the bacterian antigen and the Ig. The direct immunofluorescence negativity can be due to: (1) The IC being rapidly eliminated by the neutrophils; (2) the fact that these are nonimmunologic pathologic cases. On the other hand, the IC deposit could be a passive phenomenon in a previously damaged vessel. With great frequency, mixed cryoglobulinemia is associated with systemic conditions of the auto-immune type (collagenosis, etc) or of the malignant lymphoid haemopathy type, and with NMA. With what frequency is mixed cryoglobulinemia found in the NMA? 33% of the 47 cream's cases. What is the pathogenic relationship between processes? Often the cryoglobulin components are found deposited in angiitis lesions, but its presence and intensity does not guard any relationship with the cryoglobulinemia rate. Besides the 33% of the cases with mixed cryoglobulinemia, 13% serum's anti-complementary activity, and the remaining 54% had no indications of circulating IC with the usual techniques. Of 104 cases of Schónlein-Henoch purpura, 75 of which had nephritis, only 10% had hypocomplementemia. In summary, in about 50% of the patients with NMA, no reasonable indication of IC disease was found...

Viral replication was studied in 7 cases of PAN associated with hepatitis B virus (HBV). Serum and liver were strongly positive for markers reflecting HBV replication (constant high levels of HBe Ag, numerous hepatocytes nuclei reactive for HBc Ag, high DNA-polymerase activity). No cases were found to be positive for delta antigen or antibody. Mild biological and histological signs of liver damage were present in all patients but one. In PAN, high replication might lead to continuous stimulation and formation of circulating immune complexes in antigen excess which deposit in vascular walls with subsequent vasculitis. The demonstration of intense and permanent HBV replication could explain the unsatisfactory results observed with steroids and immunosuppressive drugs. Since steroids have been shown to increase HBV replication, this therapy might contribute to the perpetuation of the immunopathogenic process responsible for PAN. A more rational approach should take advantage of new antiviral drugs inhibiting HBV replication as suggested by preliminary beneficial results.

In examination of the ultrastructure of excised tissue and other material from patients with various diseases, principally dermatovenerological affections and with malignant tumors, and in healthy control subjects, patterns suggesting mycoplasma were repeatedly found in certain diseases only. Specific attempts to isolate mycoplasma from the material were made, in which previously patterns of a mycoplasma type had frequently been seen. It was possible to culture mycoplasma-like organisms in vitro from patients with the following diseases: malignant melanoma, mycosis fungoides, prickle cell carcinoma, squamous cell carcinoma, non-specific urethritis, pemphigus erythematosus, panarteritis nodosa and vasculitis allergica cutis.

Lymphomatoid granulomatosis is a necrotizing arteritis primarily affecting the lungs but also found in the skin, kidneys, central nervous system, and other extra-pulmonary sites. Cutaneous involvement occurred in 45% of the cases described by Liebow in his original series. Light microscopy studies were performed. The IgA and IgG levels were slightly decreased and the IgE level was elevated. Cell-mediated immunity was impaired. No viruses were isolated or identified by immunofluorescence. A man had cutaneous lesions as the first sign of lymphomatoid granulomatosis.

Two cases of systemic necrotizing angeitis are reported because of their very unusual presenting symptom: serous otitis media responsible for bilateral deafness. After this "invasion phase", typical polyarteritis nodosa developed. Cardiac involvement, with auriculoventricular block, and cranial neuritis were observed in both cases. The few previously published identical cases are reviewed. Specific neurological and cardiac forms of P.A.N. are discussed. It is hypothesized that the cause of this immune complex-mediated disease is infectious.

A nineteen-month-old child presented with a febrile illness, skin rash, painful swelling of the joints, lymphadenopathy and hepatosplenomegaly. Pseudomonas was cultured from the blood during life and, subsequently, at autopsy. Autopsy revealed a generalized panarteritis involving the coronary, retroperitoneal and pulmonary arteries with thickening of arterial walls and narrowing of the lumina. Thrombi and foci of necrosis and infarcts were found in many organs. Numerous bacilli were present in fresh lesions, but not in the organizing lesions. Periodic acid-Schiff-positive deposits were found in occasional macrophages, in walls of affected vessels, in the marginal sinuses of lymph nodes and diffusely in epicardial and retroperitoneal adipose tissue. The findings suggest that some or even all cases of Kawasaki's disease and infantile polyarteritis nodosa may be caused by Pseudomonas sepsis. It is also suggested that the vasculitis and paucity of inflammatory reaction in many cases of Pseudomonas sepsis might be related to the fact that many strains of Pseudomonas produce high-molecular-weight levan (or another polysaccharide). This compound is known to inhibit the inflammatory reaction and to increase bacterial pathogenicity.