Antineutrophil Cytoplasmic Antibodies Pattern Research Articles

The role of ANCA in the management of cocaine-induced midline destructive lesions or ENT pseudo-granulomatosis with polyangiitis: a London multicentre case series.

In this multicentric study involving three London hospitals, we compared ANCA-positive and ANCA-negative cocaine-induced midline destructive lesions (CIMDL) patients to assess how presence of antineutrophil cytoplasmic antibodies (ANCA) may correlate with disease severity. Our secondary aims are to better classify etiology centered around ANCA positivity and, consequently, better disease management. A retrospective review was performed to identify patients with CIMDL seen between January 2019 and December 2022. Population data including age, sex, presentation, endoscopic findings, duration of cocaine use and active use of cocaine, type of treatment, laboratory (including ANCA serology), radiological, and histological findings were collected. Forty CIMDL patients (25 male, median age of 42 years) were identified. The majority of them (72.5%) presented with either a septal perforation, a saddle nose deformity (22.5%), and/or a palatal fistula (20.0%). ANCA was positive in 71.1% of cases (66.7% p-ANCA). No statistically significant differences in the general characteristics, type of treatment, laboratory results, radiological or histological findings were observed when comparing ANCA-positive and ANCA-negative CIMDL patients or when comparing p-ANCA and c-ANCA patients. Similarly, no statistically significant difference was obtained when comparing the pattern of distribution of lesions between the two groups. A large percentage of CIMDL patients showed positive ANCA test (71.1%) and in the majority of the cases a p-ANCA pattern specifically targeting PR3 (p-ANCA, PR3 + MPO-). However, ANCA positivity or presence of a specific ANCA pattern wasnot associated with more severe presentation or more aggressive disease. Given its similarities to granulomatosis with polyangiitis (GPA), we recommend the use of the term "cocaine-induced ENT pseudo-GPA" instead of CIMDL. IV Laryngoscope, 134:2609-2616, 2024.

FRI339 Hypophysitis Secondary To Small Vessel Anca Vasculitistreated With Rituximab

Abstract Disclosure: A. Rivadeneira: None. N. Kumar: None. S. Banerjee: None. M. Gubbiotti: None. D. Yoshor: None. J. Kharlip: None. C.A. White: None. Introduction: Granulomatosis with polyangiitis (GPA) is an autoimmune small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs) that rarely involves the pituitary. Conventional treatment of GPA includes high dose glucocorticoids with cyclophosphamide. Rituximab has been used in refractory cases with high rates of remission. We present a case of pituitary GPA treated with and excellent response to rituximab. Case: 51-year-old woman with hypothyroidism, post I-131 treatment for Graves’ disease. Patient presented with 1 year of worsening fatigue, myalgias, frontal headaches, sinus congestion and epistaxis. CT sinus showed pituitary enlargement and chronic mucosal disease. MRI pituitary showed diffusely enlarged pituitary with non-visualized posterior pituitary bright spot and thickened stalk. CT chest showed 18x11 mm nodular opacity and peribronchial fibrosis. Laboratory evaluation showed ACTH 26.7 pg/mL, cortisol 13.4 mcg/dL, TSH 1.1, T4 9.7, prolactin 53 ng/dL, estradiol <20, LH 4, FSH 23. Sodium 140 and urine osm 488. There was positive p-ANCA staining and elevated serum anti-proteinase 3 antibody (PR3), 74 units (0-20). Myeloperoxidase antibody was not elevated. ESR 73 mm/h (0 - 30) and CRP 7.9 (<7.4). Due to atypical ANCA pattern (p ANCA typically is associated with MPO not PR3), pituitary biopsy was performed and showed adenohypophysis with dense lymphoplasmacytic infiltration with nodularity of the inflammatory infiltrates, some arranged peri vascularly, compatible with involvement of the pituitary gland by GPA. She began rituximab 375 mg/m2 weekly for four weeks with plan to continue every 6 months. After treatment, the patient experienced resolution of daily frontal headaches, congestion, cough and epistaxis. CT chest showed improvement of prior lung findings, and ESR/CRP normalized. Repeat pituitary MRI is pending. Discussion: Pituitary involvement is uncommon in GPA, occurring in only 3.9% of cases. It may lead to partial or complete pituitary dysfunction, particularly central diabetes insipidus (87.5%) and hypogonadism (75%). Typical MRI abnormalities include diffusely enlarged pituitary gland, thickened pituitary stalk and absence of posterior bright spot. Treatment of GPA includes a combination of corticosteroids, Cyclophosphamide, Azathioprine and Rituximab. Remission is achieved in up to two thirds of patients. Treatment of lymphocytic hypophysitis, another common cause of diffuse pituitary enlargement, relies on high dose glucocorticoids, leading to many side effects and taper is limited by worsening symptoms. This case highlights the critical role in serologic evaluation and targeted pituitary biopsy to identify the specific etiology of pituitary infiltration to help guide alternate treatment options, and the emerging role of Rituximab as a steroid sparing agent for treatment of pituitary inflammation. Presentation: Friday, June 16, 2023

Clinical analysis of 15 cases with myeloperoxidase antineutrophil cytoplasmic antibody associated hypertrophic pachymeningitis

To study the clinical features of myeloperoxidase(MPO) antineutrophil cytoplasmic antibody (ANCA) associated hypertrophic pachymeningitis (HP). Clinical data of 15 cases diagnosed with MPO-ANCA vasculitis complicated with HP were retrospectively analyzed. Nine cases were males and the other 6 were females, with an average age of (58±8) years. All cases presented with chronic headache. Contrast-enhanced magnetic resonance imaging (MRI) scan showed local or diffused thickening of cerebral and/or spinal dura matter while brain parenchyma were normal. Nine cases developed multiple cranial nerve paralysis, with trigeminal nerve and auditory nerve involved most commonly. The main clinical manifestations were facial pain, hearing loss and tinnitus. Two cases were complicated with hypertrophic spinal pachymeningitis (HSP) and 4 cases were complicated with pulmonary diseases. Positive serum perinuclear pattern ANCA (pANCA) and MPO could be found in all cases, positive serum IgG4 was seen in two patients. erythrocyte sedimentation rate(ESR;25-116 mm/1h) and C-reactive protein (CRP;29.02-146.00 mg/L) were both elevated in 14 cases. Nine cases had elevated intracranial pressure[180-235 mmH2O (1 mmH2O=0.009 8 kPa)] and abnormal protein level (457.6-3710.0 mg/L) in cerebrospinal fluid. Six cases were treated with glucocorticoids (prednisone 20-60 mg/d) and 9 cased with glucocorticoids and immunosuppressants (methotrexate 15 mg/week or cyclophosphamide 100 mg/d po). All patients achieved remission. MPO-ANCA associated HP is a special type of central nervous system involvement in ANCA associated vasculitis (AAV). It rarely involves the lung or kidney. Steroids and immunosuppressive agents are effective. In HP with unknown underlying diseases, it is suggested to screen ANCA and IgG4 tests for AAV or IgG4-related disease.

Anti-neutrophil cytoplasmic antibody testing by indirect immunofluorescence: Computer-aided versus conventional microscopic evaluation of routine diagnostic samples from patients with vasculitis or other inflammatory diseases

BackgroundDetection of anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence assays (IFA) is of diagnostic importance in vasculitides and some other inflammatory diseases. Automation of IFA may be beneficial in high-throughput clinical laboratories. An analytical appraisal of the EUROPattern (EPa) automated microscope and image analysis system has not been reported in a routine clinical laboratory setting testing samples from both vasculitis and non-vasculitis patients. MethodsResults of EPa and on-screen ANCA pattern recognition of 568 consecutive routine serum samples were compared to those of conventional visual evaluation. ResultsAgreement of discrimination between negative and non-negative samples was 86.1% comparing EPa and conventional reading, and it increased to 96.7% after on-screen user validation. Importantly, from the 334 samples classified as negative by EPa 328 (98.2%) were also negative by conventional evaluation. Pattern recognition showed ‘moderate’ agreement between classical microscopic and EPa analysis (κ = 0.446) and ‘very good’ agreement after user validation (κ = 0.900). Misclassification by EPa was dominantly due to the presence of anti-nuclear/cytoplasmic antibodies (incorrect pattern, 80/568) and the lower fluorescence cut-off of the automated microscope (false positives, 73/568). ConclusionsAutomated ANCA testing by EPa is a reliable alternative of classical microscopic evaluation, though classification of sera needs correction by trained personnel during on-screen validation.

P099 LEUKOCYTOCLASTIC VASCULITIS AFTER USTEKINUMAB INDUCTION IN CROHN’S DISEASE: A CASE SERIES AND SYSTEMATIC REVIEW

Abstract Ustekinumab (UST) is an effective treatment for Crohn’s disease (CD). Here we present two cases of leukocytoclastic vasculitis (LCV) in CD patients after UST induction therapy with a review of the literature. Patient #1: A 26 year old woman with a 14 year history of Crohn’s ileocolitis. She was previously treated with 6-mercaptopurine, infliximab, and vedolizumab without durable response. She ultimately underwent a left hemicolectomy due to development of a sigmoid stricture and was started on UST postoperatively. Thirty-six days after her initial UST intravenous (IV) infusion of 390 milligrams (mg) she developed new partially blanching, erythematous, non-tender, non-pruritic macules and papules over the right medial thigh, which later evolved into palpable purpura involving both lower extremities (Figure 1A). She reported no gastrointestinal (GI) or other symptoms. White blood cell (WBC) count and metabolic panel were normal. Antinuclear antibody (ANA) titer was 1:80. Perinuclear pattern antineutrophil cytoplasmic antibodies (p-ANCA) were positive. C-reactive protein (CRP) was elevated to 41.5 mg/liter (L). One lesion was biopsied, and pathology findings were consistent with LCV (Figure 1B). She was started on colchicine 0.6 mg daily with improvement in her rash and has received her second dose of UST without further complications. Patient #2: A 29 year old woman with a 6 year history of Crohn’s ileocolitis. Her prior treatments include budesonide, mesalamine, and infliximab. While on infliximab, she developed jejunal and ileal ulcers on video capsule endoscopy. Infliximab was discontinued, and UST was started. Three months following initial IV induction therapy of UST, she developed pink purpuric papules and hemorrhagic vesicles involving her bilateral shins, dorsal feet, calves, and bilateral extensor forearms. The appearance of the rash was consistent with LCV (Figure 2). She was started on prednisone at 60 mg daily for 1 week with taper resulting in complete resolution of her rash. UST was continued with no recurrence. WBC count and metabolic panel were normal. ANCA was negative, and ANA titer was 1:80. CRP was elevated to 13.2 mg/L. Literature review revealed only one prior published case report of a patient with inflammatory bowel disease developing LCV after administration of UST. In this case, UST was discontinued since re-administration caused the rash to return. Here we have two patients who developed LCV soon after initiating UST therapy, although after treatment with prednisone/colchicine, there was no recurrence with continuing UST. It is possible to develop LCV in association with CD alone; however, these patients had longstanding disease without occurrence of LCV until being started on UST. Moreover, patient #1, was in remission from a Crohn’s disease standpoint at the time of UST initiation and onset of the rash.

The significance of ANCA positivity in patients with inflammatory bowel disease

Traditionally anti-neutrophil cytoplasmic antibodies (ANCA) are used to subtype patients with inflammatory bowel disease (IBD) and to predict primary sclerosing cholangitis (PSC). The clinical utility of this testing in the Australian context is not known. Our retrospective, cross-sectional study looked at the results of ANCA testing performed during routine clinical review and aimed to retrospectively review (1) the distribution of different ANCA subtypes for IBD patients, (2) the temporal change of ANCA status, and (3) the predictive value of ANCA forPSC. Sixty-four IBD patients attending our hospital gastroenterology clinic between 2012 and 2016 had at least one ANCA test requested. Surprisingly, >80% of the IBD patients in our cohort who underwent ANCA testing had a positive ANCA result and a significant proportion had positive PR3 antibodies. However, no specific ANCA pattern predicted a specific IBD subtype or clinical course. Pairing ANCA and anti-Saccharomyces cerevisiae (ASCA) did not add value in subtyping IBD for these patients. Our study suggests that there is little value in ordering an ANCA for patients with IBD.

ANCA associated vasculitis in patients from Saudi Arabia.

Objective:To explore clinical and laboratory features, therapy and outcome of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) patients from our tertiary care center.Methods:This study of AAV patients seen in Rheumatology clinics at King Khalid University hospital (KKUH), King Saud University, Riyadh during the period 1990-2014 was carried out retrospectively. Demographic, clinical, haematological and immunological parameters along with therapy, complications and outcome were retrieved from patients' medical charts. Different characteristics were compared between the three groups of AAV; GPA (Granulomatosis with polyangiitis), MPA (Microscopic polyangiitis) and EGPA (Eosinophilic granulomatosis with polyangiitis).Results:We identified 34 AAV patients (21 males: 13 females; 31 Saudis: 3 non-Saudis) comprising of 23 GPA, 2 MPA and 9 EGPA cases. The mean age of onset was 42.1±17.6 years (range 11-75) and mean duration of disease was 8.7± 5.1 years (range 1-20). The most frequently affected system was pulmonary in all AAV (73.5%), GPA (65.2%) and EGPA (100%) while it was renal in MPA (100%) patients. Ophthalmological and upper airways involvement was higher in GPA. Neurological involvement was higher in EGPA (p<0.05). ANCA were detected in 79.4% of AAV patients, of them c-ANCA were 77.8% and p-ANCA 22.2%. ANCA was positive in 91.3% GPA, 100% MPA and 44.4% EGPA patients. In GPA c-ANCA were detected in 80.9% and p-ANCA in 17.4%, in MPA, c-ANCA were detected in 50% and p-ANCA in 50%, in EGPA, c-ANCA were observed in 75% and p-ANCA in 25%. GPA patients had PR3 specificity in 93.3%, and MPO in 6.7%, PR3 was present in all MPA patients (100%), while EGPA patients had MPO (100%). Therapy administered were corticosteroids (100%), intravenous cyclophosphamide (58.8%), azathioprine (50%) and rituximab (11.8%). Infections were noted in 29.4%.Conclusions:The 10-year survival in our AAV patients was 95%. ANCA pattern was similar to Caucasian AAV patients and different from Japanese and Chinese AAV patients.

Cytoplasmic Pattern Anti-neutrophil Cytoplasmic Antibody (cANCA)-positive Cutaneous Leukocytoclastic Vasculitis Induced by Propylthiouracil: A Case Report

Propylthiouracil (PTU) is a medication commonly used to treat hyperthyroidism, but it has various rare side effects such as anti-neutrophil cytoplasmic antibodies (ANCA)- associated vasculitis (AAV). In the last decades, multiple cases of PTU-induced AAV have been reported, some being fatal. While AAV is primarily related to perinuclear-staining ANCA/anti-myeloperoxidase (pANCA/anti-MPO), it can occur to a lesser extent in association with cytoplasmic staining ANCA/ proteinase 3 (cANCA/PR3). A case is presented of a 62-year-old female with a history of hyperthyroidism due to toxic multinodular goiter treated with a standard dose of PTU. Approximately 3 years after starting therapy, she noticed formation of skin ulcerations on both of her ear lobes, nose and bilateral limbs. Detailed hospital work-up detected cANCA positivity. Biopsy of the affected skin revealed leukocytoclastic vasculitis and additional tests excluded systemic vasculitis. The patient was diagnosed as PTU-induced vasculitis, a form of drug-induced vasculitis. Although clinical manifestations improved slightly after total thyroidectomy, the patient could not be saved because of the fulminant course of infected and disseminated skin ulcers. Conclusion: PTU is one of the causes of AAV. However, the presence of cANCA positivity when pANCA is negative in PTU-induced AAV is extremely rare. Here, we present a rather unusual case of PTU-induced AAV associated with cANCA.

Positive c-ANCA in Henoch–Schonlein purpura: what is the mechanism?

We read with great interest the recent contribution by Boulis et al. [1]. They reported a case of adult-onset Henoch–Schonlein purpura (HSP) associated with positive cytoplasmic pattern anti-neutrophil cytoplasmic antibodies (c-ANCA), but they did not explicate the possible mechanisms. We would like to suggest a possible pathomechanism of positive c-ANCA in HSP. We also studied about the prevalence of ANCA (c-ANCA and p-ANCA) in 30 Korean children with HSP and only one of them had weakly positive result of perinuclear pattern ANCA (p-ANCA), which became negative at follow-up [2]. Therefore, we think that c-ANCA or p-ANCA may not be an important serologic marker in children with HSP. Kallenberg CG described that inflammatory cytokines, such as interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha, make priming of neutrophils (membrane expression of proteinase 3 [PR3]) and upregulation of adhesion molecules on their surface as well as on the vascular endothelium [3]. They reported that primed neutrophils adhere to the endothelial cells and released PR3 can be processed and presented by antigen presenting cells (APCs) to T-helper cells [3] They also speculated that as T-regulatory cells (Tregs) cannot inhibit the autoimmune response in Wegener’s granulomatosis, autoreactive T cells might undergo repeated stimulation by PR3-pulsed APCs, and therefore, PR3-stimulated Th cells act on B cells, enhancing the production of ANCA [3]. Because it was shown that TNF-alpha levels are elevated in the acute phase of HSP [4] and regulatory T cells including CD(4?)CD(25?) Tregs were significantly lower in patients with HSP than those of controls (P 0.05) [5], there is the possibility that TNF-alpha and defective Tregs may play important role in priming of neutrophils and elevation of c-ANCA in some patients with HSP. However, because the positive results of ANCA are very rare in patients with HSP, further studies are necessary to elucidate the role of neutrophil priming and ANCA in the pathogenesis of HSP.

Spectrum of ANCA-Associated Disorders According to Serological Phenotype in Routine Care: Retrospective Case Series of 209 Patients

Objective : To summarize the experience of three years of positive ANCA (anti-neutrophil cytoplasmic antibodies) testing in a single university based hospital. We describe the clinical features according to ANCA phenotype of patients who did and did not have ANCA- associated vasculitis (AAV). Methods : We did a review of all samples tested for ANCA in a 3 year-period (2005-2007). Each sample was tested by indirect immunofluorescence (IIF) and enzyme-linked-immunosorbent assay (ELISA). Sera were considered as positive for ANCA testing if either IIF or ELISA for MPO or PR3 antigen specificity was positive. Patients were considered as having AAV on established diagnostic criteria and algorithms. Results : The positive ANCA population consisted in 209 patients, 54 were classified in the AAV group and 155 patients constituted the “Others” group. The typically most relevant ANCA phenotypes (C-ANCA/anti-PR3+ and P-ANCA/anti-MPO+) were detected in 90 % (49/54) of patients in the AAV group and only 10% (15/155) of the “Others” group (p < 0.001). Among the latter none developed AAV during follow-up. Positive IIF alone was found in 4% (2/54) of the AAV group and in 68% (105/155) of the “Others” group (p < 0.001). In patients without AAV, positive IIF alone or positive ELISA with negative IIF represented the main ANCA pattern. Conclusion : In routine clinical practice, most patients with positive ANCA testing do not have AAV. The typical ANCA pattern (C-ANCA/anti-PR3+ or P-ANCA/anti-MPO+) remains a strong predictor of AAV in patients with a high level of suspicion for systemic vasculitis. In other cases, ANCA positivity should be interpreted with extreme caution.

Orbital pseudotumor: A single precursor clinical manifestation of Wegener granulomatosis in a ten year old boy

Wegener granulomatosis (WG) is a type of vasculitis characterized by the presence of anti-neutrophil cy-toplasmic antibodies (ANCA) and inflammation of small and medium sized vessels with granulomas formation. Most commonly affected organs include upper and lower respiratory tract, kidneys, eyes, nervous system and skin. Kidneys’ involvement has a central position in the classification, diagnosis, treatment and prognosis of patients with WG, and is characterized by the presence of necrotic glomerulonephritis and clinical manifestations that vary from microscopic hematuria to acute renal insufficiency. We describe a case report of a ten year old boy presenting with microscopic hematuria of glomerular origin and a medical history of orbital pseudotumor two years before his hospitalization due to renal symptoms. Renal biopsy revealed lesions of pauci-immune glome-rulonephritis and findings of granulomatous inflam-mation and necrotizing vasculitis. Serum was positive for p-ANCA antibodies (perinuclear staining pattern ANCA antibodies). These findings led to the diagnosis of WG of generalized form (according to EULAR/ PRINTO/PRES criteria). The patient has been treated with aggressive immunotherapy with the use of ster-oids, cyclophosphamide and mycophenolate mofetil. Disease remission has been established and retained one year after initial diagnosis. Orbital pseudotumor, which is a diagnosis of exclusion, has been the initial disease’s clinical manifestation, even though at that time neither the ocular biopsy nor the immunologic workup had been indicative in terms of WG. Although WG is very rare in children, this disease should always been included in the differential diagnosis in patients with similar clinical manifestations and clinicians should emphasize on the recognition of granulomatous vasculitis in biopsies as well as on repeated tests for ANCA antibodies’ detection in serum. High morbidity and mortality rates [1] of this clinical entity necessitates the early recognition of atypical disease’s forms and the close follow up in cases of uncertain initial diagnosis.

Anti-proteinase 3 antibodies in diffuse systemic sclerosis (SSc) with normotensive renal impairment: is it suggestive for an overlapping between SSc and idiopathic vasculitis?

OBJECTIVE: To test the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic sclerosis (SSc) and to verify a possible association of ANCA with normotensive renal involvement in SSc. PATIENTS AND METHODS: 51 patients affected by SSc, 35 with diffuse scleroderma (dSSc) and 16 with limited scleroderma (lSSc), were tested for ANCA by indirect immunofluorescence (IIF) on human ethanol and formalin-acetone-fixed granulocytes (before and after DNase treatment), by conventional enzyme linked immuno-sorbent assay (ELISA) and by capture-ELISA. RESULTS: Six out of 51 selected SSc patients had ANCA by IIF (11.7%) and five presented a perinuclear/nuclear atypical ANCA pattern. In all cases we only found anti-proteinase3 (aPR3) antibodies. All ANCA positive patients had diffuse form of SSc (17.1%), all were anti-Scl70 positive (aScl70), five patients had proteinuria, three had microscopic haematuria. All ANCA positive patients were normotensive with normal renin plasma levels, the mean erythrocyte sedimentation rate (ESR) was higher in this group compared to the other SSc patients. CONCLUSIONS: Our study shows that aPR3 is not rare in dSSc. According to the clinical and serological findings and to the recent literature, we can hypothesise that when ANCA are found in SSc, an overlapping of scleroderma with systemic necrotizing vasculitis should be suspected.

Necrotizing scleritis in a patient positive for both c- and p-ANCA without underlying systemic vasculitis

Scleritis is a painful inflammatory disorder of the outer coating of the eye. Any form of scleritis associated with a systemic disease is more likely to be aggressive [1], and it is now recognized that antineutrophil cytoplasmic antibody (ANCA)-associated active scleritis tends to have more severe inflammation and requires more aggressive therapy [2]. Here, we report a case of necrotizing scleritis positive for both cytoplasmic pattern ANCA and perinuclear staining pattern ANCA without underlying systemic vasculitis, which was successfully treated with intravenous pulse cyclophosphamide therapy.

Absence of ANCA in Behçet's syndrome with large vessel involvement

The aim of this study was to examine the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA) in patients with Behcet's syndrome (BS) with large vessel involvement. The sera of 48 consecutive patients with BS with large vessel involvement, seven patients with Wegener granulomatosis (WG), and 10 healthy staff were studied for the presence of the cytoplasmic (c) and perinuclear (p) pattern of ANCA by indirect immunofluoresance (IIF). The sera were also examined for antibodies against proteinase 3 (anti-PR3) and myeloperoxidase (anti-MPO) by enzymelinked immunosorbent assay (ELISA). None of the sera from the patients with BS and healthy controls had detectable ANCAs, while all positive control sera from patients with WG showed ANCA positivity in some form. This study confirms that there are no detectable ANCAs in patients with BS with large vessel involvement by IIF and ELISA tests.

A 44‐year‐old woman with cutaneous bullae and extensive skin necrosis

Five weeks before presentation, the patient had experi-enced a cough and mild dyspnea. She was diagnosed withpneumonia, completed a 7-day course of ciprofloxacin anddoxycycline, and her respiratory symptoms resolved.Three weeks before presentation, the patient had reportedfevers, chills, diaphoresis, arthralgias, and myalgias, anddeveloped a small erythematous lesion on her left breast.The lesion subsequently enlarged and became hemor-rhagic. She simultaneously developed additional lesionson her chest, abdomen, arms, and back. The largest ofthese, located on her left arm, was 15 cm in diameter. Allof the lesions were exquisitely tender. She was hospital-ized at an outside hospital for 5 days and given a diagnosisof cocaine-induced vasculitis. Upon discharge, she wasinstructed to abstain from cocaine and was prescribedtrimethoprim/sulfamethoxazole for a possible cellulitis in-volving the skin lesions.Ten days after discharge from the outside hospital, thepatient presented to our institution for pain managementand further evaluation. The rash had progressed since herearlier discharge. She had continued to use cocaine, her-oin, and prescription opioids. She had last smoked co-caine 3 days before presentation and last used intranasalheroin 1 week before admission. She reported acquiringcocaine from a new supplier 2 weeks before her rash hadbegun.

Wegener’s granulomatosis: experience from a Brazilian tertiary center

Most epidemiological studies with Wegener's granulomatosis (WG) patients are based on populations from the Northern hemisphere, whereas very few studies have been conducted in Southern hemisphere populations, particularly from South America. The authors performed a large retrospective, demographic study including clinical and laboratory profiles of 134 consecutive WG patients seen at one Brazilian center from 1999 to 2009. Mean age at initial WG diagnosis was 43.4 +/- 15.5 years, and mean disease duration was 8.6 +/- 6.6 years. Sixty-four (47.8%) patients were male and a total of 113 (84.3%) subjects were white. Ear/nose/throat involvement occurred in 85.8%. The classic lung and renal involvement were observed in 77.6% and 75.4%, respectively, followed by ocular (35.8%), musculoskeletal (33.4%), cutaneous (29.1%), neurological (20.1%), cardiac (11.2%), and genitourinary involvement in 2.2% of cases. Cytoplasmic pattern-antineutrophil cytoplasmic antibody was detected in 83 (61.9%) cases. Ten (7.5%) individuals presented limited forms of WG. Classic therapy with corticosteroids and cyclophosphamide was used in 97 cases (72.4%). There were no cases of tuberculosis or Pneumocystis jiroveci pneumonia, but cutaneous herpes zoster occurred in eight (6.0%) individuals. There were 29 deaths (21.6%). Eighteen patients died of septic shock (mainly bacterial pneumonia), whereas four died of alveolar hemorrhage, four of myocardial infarction, and three of other causes. In summary, our data from a very large retrospective and descriptive study mirrored the main clinical features of WG described in other countries, demonstrating that they may serve as a reference for South American populations.

Pauci-immune Crescentic Glomerulonephritis Associated With ANCA of IgA Class

Pauci-immune renal vasculitis is associated strongly with antineutrophil cytoplasmic antibodies (ANCAs) of the immunoglobulin G (IgG) class, which are detected in 80% to 90% of affected patients. IgA ANCAs have been reported in association with various conditions, but never in the setting of pauci-immune vasculitis. A 28-year-old man with unexplained polyclonal hyper-IgA1 diagnosed in childhood presented with decreased kidney function, nephrotic syndrome, and microscopic hematuria. Kidney biopsy showed pauci-immune crescentic glomerulonephritis. Serum test results were negative for IgG ANCA by means of both indirect immunofluorescence and enzyme-linked immunosorbent assay techniques. Conversely, indirect immunofluorescence performed using anti-IgA antibody was strongly positive with a cytoplasmic ANCA pattern, and an enzyme-linked immunosorbent assay test had positive results for both antimyeloperoxidase and anti-proteinase 3 IgA. IgA ANCAs were not detected in 2 control serum samples from 1 patient with polyclonal hyper-IgA and 1 patient with monoclonal hyper-IgA. The patient received corticosteroids and 4 weekly perfusions of rituximab (375 mg/m2). After a 6-month follow-up, decreased kidney function and nephrotic syndrome persisted and IgA ANCA titers were unchanged. However, a control kidney biopsy showed a decrease in vasculitis activity. This first case of pauci-immune vasculitis associated with ANCA of the IgA class suggests the potential pathogenetic role of these peculiar antibodies. Additional studies are needed to determine whether IgA ANCAs, which are not routinely screened for, can be detected in patients with pauci-immune vasculitis either alone or in association with IgG ANCA.

Difficulty of diagnosing Wegener's granulomatosis in the head and neck region

Objective The objective of this study was to review the various clinical features associated with Wegener's granulomatosis (WG) in the head and neck region and to discuss the difficulty of diagnosing patients with early stage WG. Methods Between January 1998 and August 2007, WG was diagnosed and treated in 16 patients at the Department of Otolaryngology, Hyogo College of Medicine. Clinical and operating records of these patients were analyzed retrospectively. Diagnosis was based on the Japanese criteria proposed by the Japanese Ministry of Health and Welfare in 1998. Results Ten patients (62.5%) had a definite diagnosis of WG, and the other six patients (37.5%) had a probable diagnosis of WG. The period from the onset to diagnosis was between 1 month and 30 years. The generalized form of WG was observed in three patients (18.8%), and the limited form of WG was observed in the other 13 patients (81.2%). Nasal, aural, and ophthalmic symptoms were initially presented in 10, 3, and 3 patients, respectively. Cytoplasmic pattern antineutrophil cytoplasmic antibodies (cANCAs) and perinuclear pattern ANCA (pANCA) were positively detected in 68.8% (11/16) and 27.2% (3/11) of the patients, respectively. Five of 14 patients (35.7%) had pathologic features of WG in biopsy samples from the head and neck region. Three patients in whom a diagnosis of WG was difficult are presented, and immediate lessons of our experience were discussed. Conclusions This study emphasized the difficulty of diagnosing WG, particularly at an early stage and when limited to the head and neck region. The biggest challenge faced in diagnosing WG is that it requires a high index of suspicion. When WG was suspected, we should obtain an accurate medical history from patients and repeat serologic and histopathologic examinations.

Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)

In patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, indirect immunofluorescence (IF) distinguishes between cytoplasmic (C-ANCA) and perinuclear (P-ANCA) neutrophil staining patterns. In patients with primary systemic vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome, these IF staining patterns correspond broadly with antibodies to the two major antigens: the C-ANCA pattern is associated generally with antibodies to serine protease 3 (PR3) and the P-ANCA pattern with antibodies to myeloperoxidase (MPO). However, some sera positive for ANCA by IF are negative for anti-PR3 and anti-MPO antibodies, suggesting the presence of antibodies to minor antigens of PMN granules. We tested sera from a previously well-defined clinical cohort of patients for antibodies to four possible minor antigens: bactericidal permeability increasing protein, elastase, cathepsin G and lactoferrin. IF-positive (+) sera had significantly higher antibody frequencies to the minor antigens than did the IF-negative (-) sera (P < 0.01). Patients with IF(+) PR3(-)MPO(-) sera showed the most varied reactivity to the minor antigens. Among the IF(+) groups, the IF(+) PR3(+)/MPO(-) sera showed the lowest reactivity to the minor antigens. Patients with well-defined ANCA specificities, e.g. the PR3-ANCA response associated with Wegener's granulomatosis, are less likely than are other patient subsets to have antibodies to minor antigen targets. Autoantibodies to these minor antigens contribute to the overall pattern of ANCA identified by IF and help to explain why the correlation between IF and enzyme immunoassays show discrepancies. While the pathophysiological significance of antibodies to minor target antigens needs further evaluation, they may be markers of inflammation associated with disease processes.

Eye Manifestations in Patients with Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Case Series and Literature Review

To report and summarize eye manifestations of patients with perinuclear pattern antineutrophil cytoplasmic antibody [pANCA, myeloperoxidase (MPO)-ANCA]-associated vasculitis. The medical records of four consecutive patients with pANCA (MPO-ANCA) vasculitis who showed eye manifestations were retrospectively reviewed. In addition, the medical literature databases, PubMed and Japana Centra Revuo Medicina for Japanese literature, were searched for pANCA vasculitis patients with eye manifestations. Three of the four patients treated at the Okayama University Hospital showed unilateral or bilateral scleritis. In the literature review, eight of the 27 patients showed ocular surface manifestations such as scleritis and peripheral keratitis. Other frequent eye presentations were posterior segment manifestations such as central or branch retinal vein occlusion, optic neuropathy, and acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Systemically, the most frequent manifestations were glomerulonephritis in the present patients as well as in the patients reported in the past studies. Ocular surface manifestations and posterior segment manifestations were major eye presentations in patients with pANCA-associated vasculitis. ANCA testing including both pANCA and cytoplasmic pattern antineutrophil cytoplasmic antibody would help establish a systemic diagnosis in patients with eye manifestations such as scleritis, retinal vein occlusion, optic neuropathy, or APMPPE.