Positive Antinuclear Antibody Titer Research Articles

Granulomatous Features in Juvenile Idiopathic Arthritis-Associated Uveitis is Not a Rare Occurrence.

BackgroundJuvenile idiopathic arthritis (JIA)-associated uveitis is the most common form of intraocular inflammation with systemic involvement in childhood. Textbooks tend to describe it as non-granulomatous anterior uveitis. Here, we report the percentage of granulomatous features in JIA-related uveitis among patients at a uveitis referral center.MethodsWe conducted a retrospective study of all patients with JIA-related uveitis who were seen at the Center for Ophthalmic Specialized Care in Lausanne between 2000 and 2020. The sample comprised pediatric patients with bilateral anterior uveitis diagnosed as JIA-related with positive antinuclear antibody (ANA) titers. Exclusion criteria were a positive Mantoux or Quantiferon® test or elevated serum lysozyme and/or angiotensin converting enzyme (ACE) levels. The presence of one of the following features qualified the uveitis as granulomatous: granulomatous keratic precipitates (KPs) of mutton-fat type, smaller granulomatous KPs, or Koeppe nodules. The amount of inflammation was measured using laser flare photometry.ResultsThirty-eight patients were identified (mean age 13.34 ± 2.71 years; all female). In 12 patients (31.5%), the uveitis presented granulomatous features at presentation or during follow-up in at least one eye. Two of the 12 (16%) granulomatous patients had only light or no systemic involvement. The mean flare was 136.3±149 ph/ms, which is much higher than granulomatous uveitis entities of other origin reported in the literature.ConclusionJIA related uveitis can have a granulomatous presentation in about one third of patients with the Oligoarticular type and ANA positive, seen in a uveitis referral center. The presence of granulomatous features in bilateral uveitis in ANA-positive pediatric patients should not exclude the diagnosis of JIA-related uveitis, even in the absence of systemic involvement, as this entity presents a much more severe uveitis than other granulomatous anterior uveitis entities.

S2670 Wilson Disease Presenting With Autoimmune Hepatitis Features: A Clinical Enigma

INTRODUCTION: Wilson disease (WD) is a genetic disorder that commonly presents with neuropsychiatric and hepatic symptoms due to an inherited defect in the metabolism of copper. In some cases, the presence of autoimmune hepatitis (AIH) markers despite features of WD can result in diagnostic delays. We present the case of a 25 year old woman presenting with decompensated liver cirrhosis attributed to WD with confounding factors of AIH. CASE DESCRIPTION/METHODS: A 25 year old woman presented to the emergency department with abdominal distension and bilateral lower extremity edema. Her physical exam was remarkable for abdominal ascites and bilateral pitting leg edema. Laboratory analysis demonstrated an elevated alkaline phosphatase at 211 U/L, as well as aspartate aminotransferase and alanine aminotransferase at 97 IU/L and 62 IU/L respectively. CT abdomen demonstrated small sclerotic liver with evidence for portal hypertension. Further studies were significant for a low ceruloplasmin level, positive antinuclear antibody (ANA) and low titer positive anti-smooth muscle antibodies (ASMA). She underwent upper endoscopy that revealed Grade 2 esophageal varices (Figure 1). Patient underwent liver biopsy and pathology revealed extensive bands of bridging fibrosis consistent with cirrhosis (Figure 2). Glycogenated nuclei, iron stain and alpha-1 antitrypsin test were negative with copper stain positive for occasional deposits in hepatocytes (Figure 3). After discharge, a 24 hour urinary copper level was elevated at 595μg/and dry weight copper level was 910.3 mcg/mg confirming WD. DISCUSSION: WD is a rare genetic condition that involves hepatic and neurological dysfunctions occurring in 1 to 30,000 of the worldwide population. Intriguingly, our patient did not have any neurological or psychiatric symptoms at the moment of presentation. Of note, the patient did not undergo slit lamp examination so the presence or absence of Kayser-Fleischer rings that are present in almost every patient with neurologic disease could not be determined. We report a case of a diagnosis of WD presenting with a positive ANA and ASMA initially misdiagnosed as AIH. The confounding factor of this case was the early detection of a positive ANA and ASMA suggesting AIH as the culprit for the decompensated cirrhosis. The correct identification of the etiology for this patient’s cirrhosis is critical as treatment and prognosis differ greatly between these two entities and can prevent delays in effective interventions.Figure 1.: EGD demonstrating grade II esophageal varices.Figure 2.: Liver biopsy slide with extensive thick bands of bridging fibrosis consistent with cirrhosis.Figure 3.: Liver biopsy slide showing copper deposits in hepatocytes.

Prospective analysis of antinuclear antibodies prevalence in a pan-tumor sample.

e15012 Background: Antinuclear antibodies (ANAs) constitute a spectrum of autoantibodies targeted to nuclear and cytoplasmic components of the cells considered serological markers for different autoimmune disease. However, ANAs are also presented in different types of cancers. Here, we present an exploratory analysis of ANAs patterns detected in patients with a recent cancer diagnosis. Methods: We carried out a prospective analysis of patients recently diagnosed of cancer in two centers. All were tested for ANAs from January to December 2019. Clinical-pathological features were collected from clinical reports. Results: 190 patients were included with different tumors: Lung(56.3%); colon/rectum(16.3%); head-neck(10.5%); pancreas(3.6%); stomach(3.1%); sarcoma(3.1%); urothelial(2.6%) and others( 3.6%). Most of the patients (pts) had stage IV (65.7%) and III (26.8%). Several histologies were included: adenocarcinoma(55.7%); squamous (32.6%) and others (transitional, clear cells, small cell and mesotelial/sarcoma). Chemotherapy was the main treatment (73.6%pts) followed by immunotherapy (11.5%pts), targeted therapy (6.8%pts) and chemo-inmunotherapy (3.1%pts). Among all pts included, only 13 had autoimmune disease: polymyalgia rheumatica (1pt); psoriasis (4pts), bronchial hyperreactivity (2pts) and hypotiroidism (6pts). In this cohort, we found that 60/190, 31.5%pts, showed positive ANAs (+) titers by immunofluorescence analysis. Different patterns were described according to First International Consensus on Standardized Nomenclature of ANAs. The predominant was a speckled pattern presented in 26% pts; secondly, a nucleolar pattern in 16.6% pts and CENP-F AC14 was presented in 8.3%pts. More minoritary patterns were also described. Patients with advanced lung cancer included 56.6% of ANAs (+) cases followed by colorectal cancer (11.6%). Adenocarcinoma (73,3 % pts) and squamous carcinoma (16,6% pts) were the most common histologies among ANAs (+) cases but none of the small cell carcinoma were ANA(+). The majority of ANAs (+) patients were on chemotherapy (73.3 % pts) followed by immunotherapy (16.6% pts). On the other hand, 4/13 of patients with autoimmune diseases presented ANAs(+) titers (CENT-F, scl70 and AC3 patterns). The only patient who developed a severe inmune-related toxicity was ANA negative. Conclusions: In this study, we describe the prevalence of ANAs and their patterns in a cohort of cancer patients. A complementary description of relevant clinical-pathological features in ANAs(+) subgroup is also reported.

Utility of repeated antinuclear antibody tests: a retrospective database study.

Anti-nuclear antibody (ANA) testing is frequently used as a diagnostic or screening test in patients with inflammatory or musculoskeletal symptoms. The value of repeat testing is unclear. We sought to evaluate the frequency, utility, and cost of repeat ANA testing. The main objective was to assess the positive predictive value of a repeat ANA test for the diagnosis of rheumatological conditions associated with ANA. In this retrospective cohort study, we analysed data from a single, multisite tertiary health network in Australia across a 7-year period. ANA and other autoimmune test results were obtained from the hospital pathology system with a positive ANA titre cutoff set at 1:160. Clinical information was sourced from clinical information systems on any patient who had a change in ANA result from negative to positive on repeat testing. The cost of repeated ANA testing was calculated using the Australian Government Medicare Benefits Schedule. From March 19, 2011, to July 23, 2018, a total of 36 715 ANA tests were done in 28 840 patients at a total cost of US$675 029 (2018 equivalent). 14 058 (38·3%) of these ANA tests were positive. 7875 (21·4%) of the ordered tests were repeats in 4887 (16·9%) of the patients, among whom 2683 (54·9%) had initially negative tests, and 2204 (45·1%) had initially positive tests. 511 (19·0%) of the 2683 patients with initially negative tests had a positive result on at least one repeat test, with a median time to first positive result of 1·74 years (IQR 0·54-3·60). A change from negative to positive ANA was associated with a new diagnosis in only five (1·1%) of the 451 patients with clinical information available and no previous diagnosis of an ANA-associated rheumatological condition, yielding a positive predictive value of 1·1% (95% CI 0·4-2·7). Repeat ANA testing after a negative result has low utility and results in high cost. Monash Health.

Rule-based and machine learning algorithms identify patients with systemic sclerosis accurately in the electronic health record

BackgroundSystemic sclerosis (SSc) is a rare disease with studies limited by small sample sizes. Electronic health records (EHRs) represent a powerful tool to study patients with rare diseases such as SSc, but validated methods are needed. We developed and validated EHR-based algorithms that incorporate billing codes and clinical data to identify SSc patients in the EHR.MethodsWe used a de-identified EHR with over 3 million subjects and identified 1899 potential SSc subjects with at least 1 count of the SSc ICD-9 (710.1) or ICD-10-CM (M34*) codes. We randomly selected 200 as a training set for chart review. A subject was a case if diagnosed with SSc by a rheumatologist, dermatologist, or pulmonologist. We selected the following algorithm components based on clinical knowledge and available data: SSc ICD-9 and ICD-10-CM codes, positive antinuclear antibody (ANA) (titer ≥ 1:80), and a keyword of Raynaud’s phenomenon (RP). We performed both rule-based and machine learning techniques for algorithm development. Positive predictive values (PPVs), sensitivities, and F-scores (which account for PPVs and sensitivities) were calculated for the algorithms.ResultsPPVs were low for algorithms using only 1 count of the SSc ICD-9 code. As code counts increased, the PPVs increased. PPVs were higher for algorithms using ICD-10-CM codes versus the ICD-9 code. Adding a positive ANA and RP keyword increased the PPVs of algorithms only using ICD billing codes. Algorithms using ≥ 3 or ≥ 4 counts of the SSc ICD-9 or ICD-10-CM codes and ANA positivity had the highest PPV at 100% but a low sensitivity at 50%. The algorithm with the highest F-score of 91% was ≥ 4 counts of the ICD-9 or ICD-10-CM codes with an internally validated PPV of 90%. A machine learning method using random forests yielded an algorithm with a PPV of 84%, sensitivity of 92%, and F-score of 88%. The most important feature was RP keyword.ConclusionsAlgorithms using only ICD-9 codes did not perform well to identify SSc patients. The highest performing algorithms incorporated clinical data with billing codes. EHR-based algorithms can identify SSc patients across a healthcare system, enabling researchers to examine important outcomes.

Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies.

Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored. Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab. Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.

1599 Cronkhite Canada Syndrome: A Rare Cause of Dysgeusia and Protein Losing Enteropathy

INTRODUCTION: Cronkhite Canada syndrome (CCS) is a rare, acquired polyposis syndrome associated with serious complications and a high mortality rate. Awareness regarding presenting symptoms, endoscopic findings, and pathologic features leads to early diagnosis and treatment, and improved survival. CASE DESCRIPTION/METHODS: 68 yo female with a history of alopecia totalis presented with 6 months of non-bloody diarrhea, 30 lb weight loss, and dysgeusia. Physical examination revealed complete alopecia, pitting lower extremity edema, and thinning and splitting of the fingernails. Diagnostic workup yielded marked hypoalbuminemia (albumin 1.1 g/dL), positive SS-a antinuclear antibody (titer 1:160), and elevated serum total IgG level (1,750 mg/dL). CT was notable for a thickened stomach with edematous rugae, and focal segmental colitis involving the cecum and ascending colon. Push enteroscopy showed diffusely edematous mucosa in the gastric antrum and duodenum with denuded appearing vili throughout the small bowel. Colonoscopy revealed diffuse polyposis throughout the entire colon and terminal ileum, with edematous underlying colonic mucosa. Biopsies of affected areas showed diffuse cystic dilation, edema of the lamina propria, and presence of plasma cells, compatible with CCS. The patient was initiated on total parenteral nutrition, prednisone 40 mg daily, and Imuran 75 mg daily. In follow up, she reported complete resolution of dysgeusia, reduction in diarrheal symptoms, weight gain, and improved energy level. Serum albumin level improved to 2.92 g/dL. DISCUSSION: Cronkhite Canada syndrome is a sporadic, acquired polyposis syndrome characterized by diffuse gastrointestinal polyposis and ectodermal features. It carries a 5-year mortality rate of 55% despite therapy, due to a high rate of serious complications, including malabsorption, infection, heart failure, and GI bleeding. Patients are at high risk of gastric and colorectal malignancies (10.4% and 25%, respectively), necessitating annual screening examinations. A combination of nutritional support and immunosuppression with prednisone (tapered dosing) and imuran (2 mg/kg) helps in achieving clinical remission and avoiding relapse. Expedited diagnosis and application of therapy has led to improvement in patient survival and achievement of clinical response. Therefore, improved clinician awareness of disease manifestations, pathologic findings, and treatment regimen is necessary to modify the disease course for this syndrome.

Yield of screening blood work and MRI of the brain and orbits in the work-up of unilateral chronic optic neuropathy.

No guidelines exist for the investigation of treatable causes of chronic optic neuropathy, including sarcoidosis, lupus, and syphilis. The purpose of this study was to determine the diagnostic yield of screening blood work (ACE (Angiotensin Converting Enzyme)for sarcoidosis, Antinuclear Antibodies (ANA) for lupus, CMIA(chemiluminescence microparticle enzyme immunoassay) for syphilis) and contrast-enhanced MRI brain and orbits in atypical unilateral chronic optic neuropathy. Retrospective review from February 2012 to June 2018 at a neuro-ophthalmology practice. Six hundred and eighty-three consecutive charts with optic neuropathy were reviewed. Inclusion criteria were unilateral chronic optic neuropathy and a work-up including contrast-enhanced MRI brain and orbits, CBC, ESR, CRP, ANA, CMIA, and ACE. Exclusion criteria were optic nerve swelling in either eye on initial assessment or an established cause of optic neuropathy. The main outcome measure was diagnostic yield. Fifty-seven patients were included. One patient had elevated ACE, seven had positive ANA titers, and three had positive CMIA. Zero patients were diagnosed with sarcoidosis, one patient was diagnosed with lupus-related optic neuropathy, and one patient was diagnosed with syphilitic optic neuropathy. The diagnostic yield of ACE was 0%, ANA was 1.75%, and CMIA was 1.75%. MRI revealed planum sphenoidale meningioma causing compressive optic neuropathy in one patient, giving it a diagnostic yield of 1.82%. Routine screening blood work (ACE, ANA, CMIA) and MRI brain and orbits for chronic idiopathic unilateral optic neuropathy has low diagnostic yield, especially if clinical suspicion for syphilis, lupus, and sarcoidosis is low. MRI should still be performed in all cases in order to rule out compressive lesions.

Cutaneous manifestations and systemic correlation in patients with lupus erythematosus and its subsets: a study of 40 cases

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; The objective was to study various dermatological manifestations and clinical and laboratory features in patients of lupus erythematosus (LE) and its subsets.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This is a cross sectional observational study done in a tertiary care hospital in a rural setup in Piparia, Ta. Waghodiya, Dist. Vadodara, Gujarat. All the patients with clinical features of LE and its subsets were included in the study over a period of 16 months and were subjected to detailed history taking, complete cutaneous and general examination and laboratory investigations.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Out of the 40 cases, 22 cases were systemic lupus erythematosus (SLE), 13 cases were discoid lupus erythematosus (DLE), four cases were of Rowell’s syndrome and one case was of mixed connective tissue disorder (MCTD). 97.5% of cases had cutaneous involvement, i.e. photosensitivity (77.5%), oral ulcers, hair loss and malar rash. Systemic symptoms and abnormal laboratory parameters were present in the cases of SLE, Rowell’s syndrome and MCTD, with hematological involvement being the most common in both SLE (77%) and Rowell’s syndrome (100%) and positive anti-nuclear antibody (ANA) titer being the most common abnormal laboratory finding in both SLE (95.4%) and Rowell’s syndrome (100%). The most commonly found antibody was anti-dsDNA (64.3%) in SLE and anti SS-A (100%) in Rowell’s syndrome.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Cutaneous features though occasionally subtle, are pointers to a diagnosis of SLE. Hair loss, malar rash and photosensitivity alone or in association with altered hematologic/ANA profile are the key markers of the disease activity.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

Scabies presenting as cutaneous nodules or malar erythema: reports of patients with scabies surrepticius masquerading as prurigo nodularis or systemic lupus erythematosus

Scabies surrepticius is a unifying term that represents non-classical presentations of scabies mite infestation. A patient with scabies surrepticius is described: a man with scabies masquerading as prurigo nodularis. The 91-year-old man had metastatic prostate cancer and presented with diffuse pruritic nodules. Prurigo nodularis was suspected; however, the biopsy revealed scabies mites in the stratum corneum. He was successfully treated with topical permethrin 5% cream and oral ivermectin. In addition, the features of a woman with scabies mimicking systemic lupus erythematosus are summarized. The 47-year-old woman had idiopathic thrombocytopenic purpura and presented with malar erythema and a positive antinuclear antibody (titer 1:320). A diagnosis of systemic lupus erythematous was entertained until skin scraping and mineral oil preparation revealed scabies mites; she was successfully treated with oral ivermectin. In conclusion, Sarcoptes scabiei infestation can present with atypical clinical morphology and an absence of classical lesions such as burrows conventionally distributed in the interdigital web spaces, volar wrists, periumbilical area, or genitalia. Scabies surrepticius is a term that has been designated to describe these unusual presentations. Prurigo nodularis and systemic lupus erythematosus can be added to the litany of conditions masquerading as scabies and are included amongst the guises of scabies surrepticius.

Choosing wisely? Multiple Sclerosis and Laboratory Screening for Autoimmune Differential Diagnoses

Abstract Background A variety of diseases can mimic the presentation of multiple sclerosis (MS). Diagnosing MS requires the exclusion of conditions considered in the differential diagnosis of MS. The guidelines of the German Society of Neurology (DGN) recommend analyzing 13 mandatory and 9 optional laboratory parameters. The mandatory recommendations include antinuclear antibodies (ANA) as well as antibodies against double-stranded DNA (anti-dsDNA Abs)). Methods In a cohort of MS outpatients, those patient records were analyzed in which test results for all or at least some of the recommended laboratory parameters were available. In addition to these laboratory parameters, MRI data, family history, clinical presentation, evoked potentials, and CSF findings were analyzed. Furthermore, a questionnaire was used to prospectively collect information about rheumatological symptoms relevant to the differential diagnosis of MS. Results In 197 of the included 554 patients, at least some of the recommended differential diagnostic laboratory parameters were available. In 59.4% of these patients, ANA titers ≥ 1:80 were detected. Neither ANA nor ANCA nor anti-dsDNA abs were able to distinguish between MS and non-MS. In 124 MS patients, 54.8% had positive ANA titers ≥1:80. MS patients with these titers suffered more frequently from autoimmune diseases and were more likely to have a family history of MS. Of the remaining 73 patients without MS, 67.1% were ANA positive. In this patient population, the ANA-positive patients were more frequently diagnosed with psychiatric diseases. In the prospectively surveyed MS patients with an ANA titer &gt;1:160, no rheumatologic disease was diagnosed during the average follow-up period of 1.9 years. Conclusion In line with the "Choosing Wisely" recommendations of the American College of Rheumatology, mandatory laboratory screening appears to offer no benefit to the initial diagnosis of multiple sclerosis, unless a specific differential diagnosis is to be excluded.

Small Duct Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a well documented disease of the biliary tract associated with inflammatory bowel diseases (IBD), especially ulcerative colitis.1 Small-duct PSC, a variant of PSC, also has an association with inflammatory bowel disease.1 The exact pathogenesis of PSC is not well understood, but thought to be due to a combination of a genetic predisposition and gut structure.1 A 34 year-old male with a history significant for rheumatoid arthritis, portal vein thrombosis and ulcerative colitis presented to the hepatology clinic for evaluation of abnormal liver enzymes. He was diagnosed with ulcerative colitis at age 24 and over the years treated with Mesalamine, steroids, Azathioprine, Cyclosporine, and Infliximab. However, he was unresponsive to therapy and underwent total colectomy 2 years after diagnosis. The liver enzymes of concern had a mixed cholestatic and hepatocellular pattern with ALT 203, AST 104, Tbili 1.7, Dbili 0.6, and ALP 339. Hence, the differential was initially broad including possible autoimmune causes, vascular with the portal vein thromboses history, drug induced or primary sclerosing cholangitis (PSC) or primary biliary cirrhosis. A viral hepatitis screen was negative. Autoimmune testing revealed a positive anti-nuclear antibody titer. Magnetic resonance cholangiopancreatography (MRCP) revealed hypoattenuations correlating with his history of portal vein thromboses. Liver biopsy revealed small duct PSC. He is scheuled for imaging every 6 months to observe for cholangitis. A retrospective analysis of patients with PSC from 1980 to 2010 at 37 centers in Europe, North America, and Australia was completed by the International PSC Study Group.2 Of the 7121 patients, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point.2 Small-duct PSC was associated with a lower risk of liver transplant, death or malignancy compared with classic PSC.2 Small-duct PSC characterized a low-risk phenotype in both sexes.2 This suggests that small duct PSC is usually seen in younger individuals, in early stage disease, and suggests better outcomes.

Treatment of SLE and Secondary Sjogren’s Syndrome with Belimumab

Belimumab neutralizes the soluble form of B-cell activating factor and is FDA-approved for treating Systemic Lupus Erythematosus (SLE). In this retrospective analysis 16 female SLE patients had been treated with belimumab according to FDA guidelines along with any immunosuppressive drugs or antimalarial drugs they had previously been prescribed, in addition to prednisone. Thirteen of 16 patients presented with serologic evidence of positive anti-nuclear antibody titer while several other SLE patients also had clinical evidence of secondary Sjogren’s Syndrome (2°SS), the latter supported by sicca symptoms and positive anti-Sjogren’s-syndrome-related antigen A antibody titer. Changes in the SLE symptoms after belimumab therapy was assessed by the recipient’s responses on the Short Form-36 questionnaire. Ten of the 16 SLE patients reported a decrease in arthralgias or in symptoms of arthritis while fatigue was reduced in 9/16 patients. However, SLE patients with sicca symptoms failed to show any change in the Short Form-36 score after treatment with belimumab. In conclusion, although the results in this small cohort study supported the use of belimumab as an adjunctive therapy for SLE, sicca symptoms associated with 2°SS did not appear to respond to belimumab.

New Tender Nodules After Arthroscopy

A woman in her 20s with a medical history significant for systemic lupus erythematosus (SLE) presented with tender erythematous nodules after undergoing right knee arthroscopy (Figure, A). SLE had been diagnosed ten years previously after she presented with a positive antinuclear antibody titer (most recent titer, 1:1280), arthralgias, leukopenia, oral ulcers, and a malar erythematous eruption. There was no history of discoid or tumid lupus lesions. Initially, the lesions were thought secondary to soft-tissue infection and were treated with courses of clindamycin, vancomycin, and doxycycline. Physical examination revealed poorly demarcated erythematous plaques and nodules, tender to palpation, ranging from the distal thigh to the lower leg, adjacent to arthroscopy sites. Lesions around the suture sites appeared more violaceous. A punch biopsy of the lesion was performed (Figure, B and C). B A

Systemic Symptoms in the Progression of Cutaneous to Systemic Lupus Erythematosus

Patients with cutaneous lupus erythematosus (CLE) who develop systemic lupus erythematosus (SLE) may have few and mild systemic symptoms. To characterize the types and severity of systemic symptoms in a longitudinal cohort of patients with CLE. Prospective, longitudinal cohort study of 77 patients with CLE who presented between January 2007 and April 2011 at a university autoimmune skin disease clinic. Systemic symptoms and severity were determined from data recorded at each study visit and from medical records. Of 77 patients with CLE, 13 (17%) went on to meet criteria for SLE, with a mean (SD) time from CLE diagnosis to SLE of 8.03 (6.20) years. Of the 13 patients, 1 (8%) solely met the mucocutaneous American College of Rheumatology (ACR) criteria of malar rash, discoid rash, photosensitivity, and oral ulcers, and 3 (23%) met the mucocutaneous ACR criteria plus positive antinuclear and other antibody titers. After a mean (SD) follow-up time of 2.81 (1.34) years, only 5 of the 13 patients with CLE (38%) who progressed to meet SLE criteria developed moderate to severe additional systemic disease. Patients with CLE who developed SLE during our study did so mostly by meeting the mucocutaneous ACR criteria, and the majority developed none to mild additional systemic disease during the study period. Thus, our study suggests that a small percentage of patients with CLE eventually develop SLE and that even if they do, most patients will have mild systemic disease.

Isoniazid Hepatotoxicity Requiring Liver Transplantation

A 65-year-old female Peruvian immigrant was initially evaluated for potential initiation of anti-tumor necrosis factor (TNF)-a therapy for her poorly controlled rheumatoid arthritis. The patient had a history of thyroid cancer that had required thyroidectomy and replacement levothyroxine. The patient’s quantiferon test was positive, and she also had a history of aspartate transaminase (AST) and alanine transaminase (ALT) values between 40 and 60 IU/ L for at least the previous 4 years. Previous laboratory evaluation had revealed a positive anti-nuclear antibody (ANA) titer at dilution of 1:640 with homogeneous pattern, positive anti-smooth muscle antibody, and elevated immunoglobulin G (IgG) levels at 2,310 mg/dL. The patient, however, denied any prior history of chronic liver disease; consequently, no further evaluation was pursued. Isoniazid (INH) prophylaxis for latent tuberculosis infection (LTBI), was instituted for an expected nine-month course. The patient did not take any dietary or herbal supplements and did not drink alcohol. One month after initiating INH, the patient sought evaluation for jaundice, nausea, and fatigue. Her total bilirubin level was 11.3 mg/ dL, direct bilirubin level 8.6 mg/dL, AST 1,642 IU/L, ALT 1,576 IU/L, alkaline phosphatase 246 IU/L, albumin 3.0 g/ dL, and international normalized ratio 1.2. Serologic testing for acute viral hepatitis was negative. Because of presumed INH hepatotoxicity, INH was discontinued. Two weeks later, the patient complained of worsening nausea as well as new-onset ascites and lower extremity edema. Her total bilirubin was 27.8 mg/dL, direct bilirubin 21.6 mg/ dL, AST 726 IU/L, ALT 588 IU/L, alkaline phosphatase 254 IU/L, albumin 2.4 g/dL, and international normalized ratio 1.8. Triphasic contrast CT imaging demonstrated a shrunken and nodular liver and moderate-volume ascites. The patient was treated with spironolactone, furosemide, and subcutaneous vitamin K, but continued to feel poorly. Two weeks later, she developed encephalopathy with worsening renal insufficiency and international normalized ratio rising to 2.3. She was transferred to Stanford Hospital for urgent liver transplant evaluation. Upon transfer, WBC was 14.2 K/lL, platelet count 112 K/lL, sodium level 126 mmol/L, potassium level 5.4 mmol/L, CO2 18 mmol/L, BUN 57 mg/dL, creatinine 2.9 mg/dL, AST 229 IU/L, ALT 251 IU/L, total bilirubin 26.1 mg/dL, alkaline phosphatase 502 IU/L, albumin 1.4 g/dL, and international normalized ratio 2.6. The patient’s model for end-stage liver disease (MELD) score was 40. Expedited transplant evaluation was initiated, and supportive care was provided with lactulose, rifaximin, and intravenous albumin. The patient also received intravenous vitamin K as well as fresh frozen plasma transfusions. Despite these measures, the patient experienced worsening encephalopathy, azotemia, and hepatic synthetic dysfunction. On E. Sheen (&) M. H. Nguyen Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, Stanford University, Alway Building, Room M-211, 300 Pasteur Drive, Stanford, CA 94305, USA e-mail: esheen@stanford.edu

A case of primary Sjögren'/INS;s syndrome presented with dysautonomia as initial manifestation

Neurological involvement occurs in 10–/INS;42% of the primary Sjö/INS;gren's syndrome (pSS). Distal sensory neuropathy is the most common, pandysautonomia without sensory neuropathy is extremely rare in the pSS as initial manifestation. We describe the case of pSS presented with bladder dysfunction, paralytic ileus and postural intolerance. /INS;A 27-year-old woman developed paresthesia in the both arms 1 week before admission and progressed paresthesia in the legs and trunk below the chest with myalgia. At admission she couldn't urinate and defecate. On examinations she was revealed with /INS;abdominal distension, decreased deep tendon reflexes and sensation for the temperature in the extremities. Autonomic symptoms and signs included no bowel sound during auscultation, increased perspiration on the whole body, bladder distension and postural intolerance with normal pupil sizes and light reflex. Abdomen CT revealed urinary bladder distension and diffuse dilated colon without obstruction suspected paralytic ileus. She had positive anti-SS-A/Ro Ab, anti SS-B/La Ab, positive anti-nuclear antibody (titer 1:40, homogeneous pattern) and anti dsDNA antibody of 38.05 IU, but with negative rheumatoid factor, anti-Sm Ab and Anti-RNP Ab. Salivary scan revealed decreased activity of both the /INS;parotid glands and sublingual glands. Motor and sensory nerve conduction studies of median, ulnar, radial, tibial, peroneal and sural nerves are mild delayed terminal latency with normal amplitude and velocity. During months her symptoms recovered without steroid or IVIG. This case suggests that pSS should be listed in the differential diagnosis of acute autonomic failure as well as chronic form.

AB0277 Antinuclear antibodies in patients with tnf- inhibitors

BackgroundDuring treatment of patients with rheumatic disease like rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA) with anti TNF-α antibodies (TNF-inhibitors) induction of antinuclear antibodies (ANA) may occur.ObjectivesThis study...

FRI0322 Diagnostic accuracy of new american college of rheumatology classification criteria for sjogren’s syndrome of 2012

BackgroundThe American-European Classification Criteria (AECC) for Sjogren’s syndrome (SS) of 2002 include the six items: I) symptoms of ocular and II) oral dryness, III) objective evidence of dry eyes (abnormal...

SAT0432 Development of Positive Antinuclear Antibodies and Rheumatoid Factor in Systemic Juvenile Idiopathic Arthritis Points toward an Autoimmune Phenotype Later in the Disease Course

BackgroundSystemic onset Juvenile Idiopathic Arthritis (JIA) is now commonly considered part of the group of autoinflammatory diseases. However, systemic inflammation tends to decrease over time, leading to a phenotype of...