Fluorescent Antinuclear Antibody Research Articles

Chronic False Positive Rapid Plasma Reagin (RPR) Tests Induced by COVID-19 Vaccination

False positive reactive plasmin reagin (RPR) reactivity following a COVID-19 vaccine has been reported, and it is therefore conceivable that individuals who receive frequent coronavirus disease 2019 (COVID-19) vaccinations may exhibit durable RPR responses. Here, we sought to investigate the extent to which repeated mRNA COVID-19 vaccines can elicit chronic false RPR reactivity in a longitudinal cohort. Participants (n = 119) in an IRB-approved (#20201026), longitudinal SARS-CoV-2 cohort study were screened for RPR reactivity via manual RPR card assays. Samples with reactive results underwent additional testing, including follow-on RPR screening at additional timepoints, confirmatory fluorescent treponemal antibody (FTA-ABS) testing and anti-nuclear antibody (ANA) testing. Medical histories were collected. We observed (n = 2) screen-positive RPR results (1.7% [2/119]) following booster vaccination, for which two individuals exhibited chronic, vaccine-induced RPR reactivity for up to 9 months following booster vaccination. Both participants were ANA-negative. It is imperative for clinicians to be mindful of the potential immunologic interference of COVID-19 vaccines with standard infectious disease assays, including RPR testing. Detailed medical histories and clinical contexts, including recent vaccination, should be reviewed prior to proceeding with distressing and invasive workups.

Clinical significance of antinuclear antibody positivity in patients with severe coronavirus disease 2019.

This study aimed to investigate the clinical characteristics and outcomes of fluorescent antinuclear antibody (FANA)-positive patients admitted for coronavirus disease 2019 (COVID-19) and identify FANA as a prognostic factor of mortality. This retrospective study was conducted at a university-affiliated hospital with 1,048 beds from September 2020 to March 2022. The participants were consecutive patients who required oxygenation through a high-flow nasal cannula, non-invasive or mechanical ventilation, or extracorporeal membrane oxygenation, and conducted the FANA test within 48 hours of admission. A total of 132 patients with severe COVID-19 were included in this study, of which 77 (58.3%) had FANA-positive findings (≥ 1:80). FANA-positive patients were older and had higher inflammatory markers and 28-day mortality than FANA- negative patients. In the multivariate Cox proportional hazard regression analysis, FANA-positive findings (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.04-6.74), age (per 1-year; HR, 1.05; 95% CI, 1.01-1.10), underlying pulmonary disease (HR, 3.16; 95% CI, 0.97-10.26), underlying hypertension (HR, 2.97; 95% CI, 1.28-6.87), and blood urea nitrogen > 20 mg/dL (HR, 3.72; 95% CI, 1.09-12.64) were independent predictors of 28-day mortality. Remdesivir (HR, 0.34; 95% CI, 0.15-0.74) was found to be an independent predictor that reduced mortality. Our findings revealed an autoimmune phenomenon in patients with severe COVID-19, which provides an ancillary rationale for strategies to optimize immunosuppressive therapy. In particular, this study suggests the potential of FANA to predict the outcomes of COVID-19.

Impact of baseline fluorescent antinuclear antibody positivity on the clinical outcome of patients with primary autoimmune hemolytic anemia

IntroductionAutoimmune haemolytic anaemia (AIHA) is an autoimmune disorder that can present in primary or secondary forms. The literature looking at impact of baseline fluorescent antinuclear antibody (FANA) positivity on outcomes of AIHA patients is infrequent. ObjectiveTo study the impact of baseline FANA positivity in patients with primary AIHA. MethodA prospective cohort study involving 29 consecutive primary AIHA patients presenting to the Haematology department from 2013 to 2015 was analysed. After recording baseline investigations including fluorescent ANA, all patients were treated as per the standard therapeutic protocols. Clinical remission, disease free survival, relapse, mortality were compared between the FANA positive and FANA Negative AIHA groups. ResultsBaseline FANA positivity was found in 17 patients (58.62%). Both the groups were comparable in terms of age, sex, Hemoglobin, LDH at presentation, number of lines of treatment needed and duration of follow up. Evan's syndrome was seen in six of FANA positive patients which was statistically significant (0 v/s 6, p = 0.023). FANA positive patients had significantly higher rates of relapse per patient month follow up (1.22 v/s 3.57, p = 0.023) and lower rates of complete response (83.33% v/s 35.29%, p = 0.0118) and relapse free survival at five years. Morbidity and mortality were numerically higher in FANA positive patients. ConclusionBaseline FANA positivity among AIHA patients was found to be associated with lower complete response rates and higher relapse rates with possible higher rates of morbidity. Presence of FANA will give us prognostic value and help us in deciding the treatment options.

Sudden-Onset Polyposis in Pediatric Patients With Ulcerative Colitis.

To the Editors: Inflammatory polyps may develop in 10% to 20% patients with inflammatory bowel disease (IBD).1 However, such patients are mostly adults, and polyps rarely develop in children. Filiform polyps are extremely rare in children with ulcerative colitis (UC).2 Herein, we present a case of sudden-onset filiform polyposis during UC treatment in an 11-year-old girl. Low-grade dysplasia was histopathologically confirmed in another single polyp; therefore, this case underlines the importance of evaluating the heterogeneity of inflammatory polyps in pediatric patients with UC and follow-up of such patients. A 9-year-old girl presented with severe anemia and hematochezia. Her blood test findings were as follows: white blood cell count, 12 620/μL (eosinophils, 10.3%); hemoglobin, 6.4 g/dL. Her QuantiFERON-TB test result was negative; furthermore, she tested negative for cytomegalovirus, herpes simplex virus, fluorescent antinuclear antibody, Clostridium difficile, and antineutrophil cytoplasmic antibodies. Her immunoglobulin E level was 260.5 IU/mL (reference range, <158 IU/mL). Moreover, her fecal calprotectin concentration was over 6000 mg/kg. Colonoscopy showed a severe UC flare-up throughout the colon. She was initially treated with corticosteroids, azathioprine, and 5-aminosalicylic acid; however, there was no symptom improvement. After 4 months, infliximab (5 mg/kg) was administered; however, diarrhea and hematochezia persisted. Her fecal calprotectin concentration was 2000 to 5000 mg/kg. Infliximab trough level and anti-infliximab antibody were 0.1 μg/mL and 25.3 ng/mL, respectively. Therefore, infliximab was discontinued, and intermittent steroid treatment was continued with cyclosporine as the main drug. Although there was no acute exacerbation of UC, complete remission could not be achieved. Colonoscopy performed 15 months later yielded findings similar to those obtained in the previous one. After 18 months, polyps that had not been seen before suddenly appeared in the form of filiform polyposis in the transverse colon (Figure 1A). Biopsy findings revealed inflammatory polyposis (Figure 1B). A single polyp (sized approximately 3 cm) was observed in the sigmoid colon (Figure 1C); histopathological examination showed low-grade dysplasia (Figure 1D). The patient underwent diagnostic exome sequencing; APC gene mutation or other IBD- or immune deficiency–related mutations were not detected. Tumor marker levels and positron emission tomography computed tomography findings indicated no evidence of malignancy in other organs.

Occurrence of Pure Sensory Neuropathy in a 45-Year-Old Female with Primary Sjögren’s Syndrome: A Case Report Study

: Complications of Sjögren’s syndrome (SS) and neuropathies may occur in some cases. Almost this complication occurs with peripheral neuropathy. Different forms of sensory neuropathy, multiple mononeuropathy, trigeminal neuropathy, multiple cranial neuropathy, radiculoneuropathy, and autonomic neuropathy can occur in SS. In this novel case presentation, polyneuropathy in a 45-year-old female patient with SS is reported with a complaint of ataxia, vertigo, dysarthria, abnormal gait, foreign body sensation, and deterioration of quadriparesis from six months ago. Fluorescent antinuclear antibody (FANA), anti-RO, anti-RO-52, and RF were strongly detected positive in her rheumatologic examination. Pure sensory polyneuropathy (ganglionopathy) was also reported in electromyography and nerve conduction velocity (EMG-NCV). Although peripheral neuropathy is the major and most common neurological aspect of neuron involvement in patients with SS, here, pure sensory polyneuropathy is reported in a 45-year-old female patient with SS. In conclusion, in this novel case presentation, a novel case of polyneuropathy concurrent with SS is demonstrated in a 45-year-old female patient.

Antinuclear antibody testing - misunderstood or misbegotten?

Antinuclear antibodies (ANAs) are a diverse group of autoantibodies that recognize nuclear macromolecules and their complexes. ANAs represent key biomarkers in the evaluation of rheumatic diseases, most prominently systemic lupus erythematosus (SLE), and ANA testing is commonly performed in the clinical setting. In addition, ANA testing is now used to assess eligibility for participation in clinical trials of new therapeutic agents for SLE. ANAs can be assayed by various techniques, with the fluorescent ANA assay often viewed as the gold standard. Whereas a positive ANA test represents a classification criterion for SLE, up to 20-30% of the healthy population, depending on the assay used, is positive for an ANA, complicating the use of this test for diagnosis or the detection of preclinical autoimmunity. Furthermore, ANAs might be expressed in SLE less commonly than often thought. This Perspectives article discusses important questions about the use of ANA testing in both the clinical and research settings.

A Case of Psoriasis Accompanied by Systemic Lupus Erythematosus.

Dear Editor: The pathologic mechanisms of systemic lupus erythematosus (SLE) and psoriasis are different: psoriasis is caused by systemic inflammatory reaction from mainly Th1 cell activation, whereas SLE is caused by Th2 cell-related abnormalities. Cases of generalized psoriasis caused by the anti-CD20 monoclonal antibody rituximab and cases of aggravation of SLE after anti-tumor necrosis factor α biologics have been reported, suggesting the immunopathologic mechanisms of these two diseases are opposite1,2. However, we experienced a case of psoriasis accompanied by SLE. A 32-year-old woman had erythematous scaly macules and patches on the trunk, inguinal area, and forehead starting one year ago (Fig. 1A, B). Medical history included arthralgia progressing since one year ago, starting from the left third finger and spreading to all fingers, wrists, toes, ankles, knees, and hips (Fig. 2A). Serologic findings were as follows: anti-SSA/Ro Ab(+), anti-Smith Ab(+), fluorescent antinuclear antibody(+), and speckled pattern. She also presented with a malar rash starting 3 months ago. On the basis of clinical and serologic findings, she was diagnosed with SLE. She was prescribed methotrexate 15 mg weekly, hydroxychloroquine 400 mg, prednisolone 5 mg, and nonsteroidal anti-inflammatory drugs, and the pain seemed to abate. To evaluate skin lesions, the forehead lesion was subjected to biopsy. Histopathologic findings were consistent with psoriasis (Fig. 1C). The skin lesions responded to topical vitamin D3 analogue and topical steroid. Arthritis was evaluated by radiography; the findings of the left hip, bilateral middle fingers, and right index finger were suggestive of psoriatic arthritis, indicating that psoriasis preceded SLE (Fig. 2B). Th17 cells can be associated with the pathogenesis of various autoimmune and inflammatory diseases by producing several effector molecules. Interleukin (IL)-17 is a potent proinflammatory cytokine produced by highly activated Th17 cells and is well known to play a major role in maintaining chronic inflammation in psoriasis. Actually, skin biopsies from patients with psoriasis exhibit high IL-17, IL-22, and IL-23 expressions3. IL-22, one of the effector molecules produced by Th17 cells, induces antimicrobial agents and β-defensins in keratinocytes and promotes epidermal hyperplasia4. This cytokine is also known to be essential for the immune barrier function of epithelial cells. Recent evidence indicates IL-17 also plays a role in the pathogenesis of SLE. Patients with SLE have higher serum levels of IL-17 and IL-23 than healthy controls3,5. Interestingly, plasma IL-17 levels are correlated with SLE disease activity5. In animal models, IL-17 is related not only to T cell-mediated tissue injury, but also to the production of pathogenic autoantibodies. In the presence of IL-17, SLE-derived B cells increase anti-DNA production5. However, the exact function of IL-17 that leads to SLE remains unknown. Besides IL-17, IL-21 produced by Th17 cells causes CD8+ T cell proliferation and induces B cell differentiation4. In summary, we report a case of psoriasis accompanied by SLE. We propose the Th17 cell-mediated immune pathway is common to both diseases. This case suggests the potential utility of treating SLE with Th17 cell-targeting agents. Fig. 1 (A) Erythematous scaly patches on the forehead. (B) An erythematous scaly patch on the inguinal area. (C) Regular elongation of rete ridges, parakeratosis, and mononuclear cell infiltration in the epidermis (HE inset: ×100). ... Fig. 2 (A) Swollen proximal interphalangeal joints on bilateral third fingers. (B) Radiograph showing marginal erosion at the right third proximal interphalangeal joint, small bony proliferation at the right index metacarpophalangeal joint, and suspicious erosion ...

Mycosis Fungoides Diagnosed with an Initial Sign Resembling Benign Dermatosis on the Upper Eyelids.

Dear Editor: Mycosis fungoides (MF) is a mature T-cell non-Hodgkin's lymphoma that presents with persistent and slowly progressive skin lesions of varying size and shape1. As the skin lesions of MF are variable, MF can be misdiagnosed as a benign dermatological condition1,2. A 21-year-old man presented with a 4-month history of skin lesions on his eyelids. The skin lesions were diffuse erythematous to violet-colored patches on both upper eyelids with multiple 1~2-mm papules scattered on the patches. Both eyelids were edematous, making the patient look like he had swollen eyes (Fig. 1A). The patient did not complain of symptoms at the lesional area but did complain of feeling weak and lethargic over the last few months. We performed laboratory tests and skin biopsy of his right eyelid, and made a preliminary diagnosis of a heliotrope rash in dermatomyositis. We decided to withhold treatment until the diagnosis was confirmed. Laboratory tests including complete blood count, liver function test, fluorescent antinuclear antibody test (FANA), and creatinine kinase showed no abnormalities. Histopathological examination revealed epidermotropic and diffuse dermal infiltration of atypical lymphocytes with some eosinophils (Fig. 1B, C); the epidermotropic and dermal atypical lymphocytes were positive for CD3 and CD4, and some lymphocytes were positive for CD30 and negative for CD20 (Fig. 1D~F). Fig. 1 (A) Erythematous papules and patches with edematous swelling on the right eyelid. (B, C) Histological specimen showing diffuse dermal infiltration of atypical lymphocytes (HE B: ×40, C: ×400). Atypical lymphocytes infiltrating ... On the second visit, an erythematous papule 5 mm in diameter (Fig. 2A) had developed on the dorsum of the right hand, and there was no improvement in the skin lesions on the eyelids. Skin biopsy of the papule showed similar histopathological findings to those of the eyelids, i.e., epidermotropism and diffuse dermal infiltration of atypical lymphocytes with some eosinophils (Fig. 2B, C). Nested polymerase chain reaction for T-cell receptor-γ gene rearrangement showed monoclonality. Fig. 2 (A) Erythematous nodules on the dorsum of right hand at the second visit. (B, C) Epidermotropism and diffuse dermal infiltration of atypical lymphocytes stained with CD4 (B: CD4, ×40; C: H&E, ×40). Bone marrow biopsy, abdominal pelvic computed tomography-multiplanar reformation, and chest computed tomography showed no internal organ involvement. With this histological and immunophenotypic information, the patient was diagnosed with MF and was treated with chemotherapy and total skin electron beam therapy. MF is the most common type of cutaneous T-cell lymphoma and accounts for half of all primary cutaneous lymphomas1. Clinically, early in the course of MF, the skin lesions may be nonspecific and variable, making the diagnosis difficult even for dermatologists1,2. A new variant of MF was recently proposed, in which papular lesions are present in the absence of patches with the presence of histopathologic features of the classic patch/plaque stage2. Moreover, advanced MF can infiltrate or metastasiaze to the eye, causing blepharitis and cicatricial ectropion3. Eyelid lesions must be differentiated from many conditions that can produce redness of the eyelids. Eczematous dermatological conditions such as contact dermatitis, atopic dermatitis, and seborrheic dermatitis commonly involve the eyelids4,5. Allergic contact dermatitis often affects the upper eyelids, while atopic dermatitis causes dermatitis in both the upper and lower eyelids. Seborrheic dermatitis is accompanied by lesions at other sites. Because the present patient had erythema and edema only on the upper eyelids without any subjective symptoms, we made an initial diagnosis of heliotrope rash in dermatomyositis. The diagnosis of MF should be made carefully on the basis of detailed history taking and physical examination if the skin lesion is persistent without changes in the shape or symptoms after conventional dermatological treatment. The present case illustrates the diversity of the cutaneous manifestations of MF, such as mimicking the heliotrope rash of dermatomyositis or eyelid eczema, and highlights the importance of skin biopsy for correct diagnosis and treatment.

Cervical Myelitis Mimicking Intractable Occipital Neuralgia

Dear Editor, Occipital neuralgia, which usually develops as a result of occipital nerve pathology, has a typical cutaneous pain distribution and a good response to peripheral nerve blockade.1 However, occipital neuralgia-like pain can sometimes be elicited by unusual structural abnormalities.2 A case of myelitis at the C2 level mimicking occipital neuralgia is described herein. A previously healthy woman aged 41 years experienced persistent electric-shock-like pain for 40 days before admission. The pain originated in the posteroinferior area of the right ear and then radiated to the right vertex area. Her symptoms were mild at first, but the severity abruptly increased 7 days after onset. The headache presented as a severe jabbing pain that was strictly unilateral and lasted for 3-4 hours, occurring about three times per day. The pain was scored at 8 on a visual analog scale ranging from 0 to 10. There were no autonomic features or skin lesions. Definitive triggering factors were not found. The pain was intractable to both medical treatment and occipital nerve block. Pain was the only symptom, and there were no other abnormal neurologic signs in any body part, including gait difficulty, voiding difficulty, sensory change, or motor weakness. Magnetic resonance imaging of the cervical spinal cord revealed a high signal lesion on the upper cervical spinal cord extending from levels C1 to C2 on T2-weighted images. The lesion was well enhanced by gadolinium and located in the right posterolateral area, involving the dorsal nerve root entry zone (Fig. 1). Cerebrospinal fluid analysis and the IgG index appeared to be normal, and an oligoclonal band was not detected. Tests of serum fluorescent antinuclear antibody, antineutrophil cytoplasmic antibody, lupus anticoagulant, human immunodeficiency virus serology, syphilis screening, segmentation rate, and vitamin B12 level yielded normal results. The patient's pain improved dramatically after intravenous injection of a high dose steroid. Given the location of the lesion, the poor response to occipital nerve blockade, and the favorable response to a systemic steroid injection, it can be concluded that cervical myelitis elicited the pain, mimicking occipital neuralgia. The greater occipital nerve arises from the sensory medial branch of the dorsal rami of the C2 spinal nerve, and its terminal branches innervate the region of the C2 dermatome.3 Hence, involvement of the C2 dorsal root can elicit pain with a distribution similar to that of the greater occipital nerve, and is clinically indistinguishable. The patient's poor response to peripheral blockade targeting the greater occipital nerve can be explained by the location of the lesion, since the dorsal root entry zone is proximal to the point of blockade. The relief of the intractable neuralgic pain provided by systemic steroid is further evidence of the relationship between the pain and myelitis. Myelitis can cause occipital neuralgia-like pain, but isolated pain without other symptoms or signs is extremely rare. To the best of our knowledge, only three cases of occipital neuralgic pain related to cervical myelitis have been reported. However, those case reports did not present detailed clinical characteristics, including the response to peripheral blockade and the anatomical relationship between the lesion and the pain.4-6 It is necessary to consider other structural causes when occipital neuralgia does not respond to conventional treatment, including occipital nerve blockade. Fig. 1 A and B: The T2 weighted MRIs show a high signal intensity lesion at C2 level. C and D: The lesion with gadolinium enhancement is located in postero-lateral area of right spinal cord involving entry zone of dorsal root.

Retroperitoneal inflammatory pseudotumor: A rare cause of prolonged fever

Introduction: Inflammatory pseudotumor of lymph node is a rare case in the etiology of fever of unknown origin. It is a rare pathology whose nosological definition is still unclear. Observation: We report the observation of a 27-year-old man presented with a two-month history of debilitating recurrent fever and weight loss. The remainder of his physical examination was unremarkable; specifically, no lymphadenopathy or organomegaly was detected. Serum protein electrophoresis was normal and fluorescent antinuclear antibody was negative. Serologic tests of Brucella species, cytomegalovirus, Epstein–Barr virus, and HIV were also negative. Numerous blood cultures were negative. Computerized tomographic scans of the chest and abdomen demonstrated mild enlargement of the retroperitoneal and iliac lymph nodes. Because of the suspicion of lymphoma, he underwent exploratory laparotomy, numerous periaortic and mesenteric lymph nodes were enlarged, and five were excised. The histologic examination concluded to a pseudotumor of lymph node. Discussion: Inflammatory pseudotumor is a benign reactive disease and rarely involves lymph nodes. Inflammatory pseudotumor arising from the lymph node was firstly reported in 1988. Any of the major lymph node groups may be involved. A single node is usually involved but multiple nodes may be affected simultaneously. Inflammatory pseudotumor of lymph node is a rare pathology whose nosological definition is unclear. It should probably be considered as belonging to a category different from the inflammatory pseudotumor of other organs. The diagnosis presents itself in case of isolated adenopathy or prolonged fever and is based on an anatomopathology.

Localized scleroderma: a clinical study at a single center in Korea

Localized scleroderma (morphea) is a rare autoimmune disease limited to the skin, characterized by cutaneous fibrosing and obstructive vasculopathy. Localized scleroderma may invade into the subcutaneous fat layer and cause permanent functional disability. Because of its rarity, there have been few clinical surveys of patients with localized scleroderma in Korea. The aim of this study was to elucidate the clinical presentation, serological data, and clinical outcomes of localized scleroderma. This was a retrospective survey conducted by reviewing available medical records during a 7year-period from 2004 to 2010 in a single medical center in Jeju Island, South Korea. In total 43 patients with localized scleroderma were included. Localized scleroderma occurred primarily in females (female to male ratio 2.6:1.0). Most patients were between 10 and 29years of age and the mean age at diagnosis was 26.2years. Plaque (51.2%) and linear morphea (37.2%) were most common. No case was associated with systemic scleroderma (systemic sclerosis). The most common site of plaque morphea was the trunk (47.8%). In the linear type, the most common site was head-neck (52.9%). Fluorescent antinuclear antibody was positive in 23.3% of all cases. Treatment included systemic corticosteroids, colchicine, anti-malarial agents, D-penicillamine or intralesional triamcinolone injection. Clinical improvement, including significant and partial response, was seen in only 62.8% of treated patients. Localized scleroderma is a chronic inflammatory condition confined to the skin. In order to exclude other conditions, thorough history taking, physical examination, serologic studies and histopathologic examinations should be conducted.

Beta-Thalassemia Minor Is Associated with IgA Nephropathy

Jung Hyun Kang, M.D., Bo Rha Park, M.D., Kyung Soo Kim, M.D., Do Yeun Kim, M.D., Hee Jin Huh, M.D., Seok Lae Chae, M.D., and Sung Joon Shin, M.D.. Ann Lab Med 2013;33:153-5. https://doi.org/10.3343/alm.2013.33.2.153

Three-Grade Classification of Photoplethysmography for Evaluating the Effects of Treatment in Raynaud Phenomenon

We assessed the utility of a 3-grade classification of photoplethysmography (PPG) with cold water provocation test in Raynaud phenomenon (RP). A total of 35 patients with RP and 38 healthy volunteers were recruited. In healthy volunteers, PPG was measured twice at intervals of 30 minutes for evaluating reproducibility of test. Percentage variation of the PPG amplitude in post- versus precold provocation was expressed on a 3-grade scale at 1, 3, and 5 minutes (reflection index: RI) in patients with RP. The improvement pattern of the PPG (IPPPG) was evaluated by summing the score differences from RI1min to RI3min and RI5min. After a therapeutic period of 8 weeks with nifedipine, the decreases in posttherapeutic RI3min and RI5min were statistically significant (P < .05). Subgroup analysis of IPPPG showed statistical significance in patients with negative fluorescent antinuclear antibody (P < .05). The analysis of cold-provoked PPG waves demonstrated and quantified improvements in peripheral arterial circulation in RP.

Comparative Study of Immunofluorescent Antinuclear Antibody Test and Line Immunoassay Detecting 15 Specific Autoantibodies in Patients With Systemic Rheumatic Disease

Based on the currently proposed algorithms, antibodies specificities (sp-ANAs) are identified mainly in samples positive for fluorescent antinuclear antibodies (FANA) screening tests. The purpose of the present study was to compare diagnostic performances of FANA and line immune assay (LIA) detecting 15 sp-ANAs in patients with systemic rheumatic diseases (SRD). In 948 sera from the patients with SRD (n = 590) and non-SRD (n = 358), we evaluated the fluorescent patterns and intensities in the FANA test, and compared the FANA results with sp-ANAs against nRNP, Sm, SS-A, Ro52, SS-B, Scl-70, PM/Scl, Jo-1, CENP B, PCNA, dsDNA, nucleosome, histone, ribosomal-P, and M2. The sensitivity and specificity was 75.9% and 52.5% of FANA test and 62.0% and 84.4% of sp-ANAs test for SRD detection. The overall agreement between FANA and sp-ANAs results was 69.2% (Kappa coefficient; 0.404). According to the clinical diagnosis, the levels of agreement varied from 33.3% to 83.1%. The positive predictive values of each FANA pattern for the detection of sp-ANAs were less than 50% except for the discrete speckled pattern (91.7%). The 1:100 intensity of FANA as well as the monoreactivity of LIA, anti-SSA(-)/anti-Ro52(+), or FANA(-)/sp-ANAs(+) was associated with non-SRD. Antibodies against ribosomal-P or PCNA were specific for systemic lupus eryhthematosus. This study highlights the need for careful interpretation of FANA test results to assess sp-ANAs and the application of sp-ANAs tests including less-common autoantibodies. In patients with clinical suspicion of SRD, screening with both FANA and sp-ANAs tests could improve diagnostic efficiency.

Treatment Response and Long Term Follow-up Results of Nonspecific Interstitial Pneumonia

The purpose of this study was to investigate the long-term clinical course of non-specific interstitial pneumonia (NSIP) and to determine which factors are associated with a response to steroid therapy and relapse. Thirty-five patients with pathologically proven NSIP were included. Clinical, radiological, and laboratory data were reviewed retrospectively. The male-to-female ratio was 7:28 (median age, 52 yr). Thirty (86%) patients responded to steroid therapy, and the median follow-up was 55.2 months (range, 15.9-102.0 months). Five patients (14%) showed sustained disease progression and three died despite treatment. In the five with sustained disease progression, NSIP was associated with various systemic conditions, and the seropositivity of fluorescent antinuclear antibody was significantly associated with a poor response to steroids (P = 0.028). The rate of relapse was 25%, but all relapsed patients improved after re-treatment. The initial dose of steroids was significantly low in the relapse group (P = 0.020). In conclusion, progression is associated with various systemic conditions in patients who show progression. A low dose of initial steroids is significantly associated with relapse.

Involvement of anticentromere antibody in interference with oocyte meiosis and embryo cleavage

The aim of this study was to investigate the clinical significance of anticentromere antibody (ACA) among types of antinuclear antibody (ANA) in the properties of oocytes retrieved from infertile women. The rate of metaphase II oocytes or embryo cleavage was significantly decreased in patients with positive ACA compared with patients with negative ACA, suggesting that ACA is an essential marker for flawed oocytes in infertile women with any type of ANA.

Clinical features and outcomes of autoimmune hemolytic anemia: a retrospective analysis of 32 cases

BackgroundThere has been no report on the clinical features or natural history of autoimmune hemolytic anemia (AIHA) in the Korean adult population. This study retrospectively analyzed the clinical characteristics and long-term outcomes of AIHA in the Korean adults.MethodsPatients newly diagnosed with AIHA between January 1994 and December 2010 at Chungnam National University Hospital were enrolled. Patient characteristics at diagnosis, response to treatment, and the natural course of the disease were documented.ResultsThirty-two patients (31 females and 1 male) with a median age of 48 years (range, 17-86) were enrolled. Of these, 21.9% were initially diagnosed with secondary AIHA. Thirteen patients (40.6%) were initially diagnosed with Evans' syndrome. Of the 29 patients who were placed on therapy, 27 (93.1%) showed a partial response or better. Nevertheless, 1 year after initiating treatment, 80% of the patients were still treatment-dependent. During follow-up (median length 14 months; range, 0.5-238), 14 of 25 patients (56.0%) who were initially diagnosed with primary warm antibody AIHA were found to have systemic lupus erythematosus (SLE). Median time to conversion to SLE was 8.0 months (95% CI, 4.3-11.7), and the probabilities of conversion at 12 and 24 months were 63% and 91%, respectively. Younger age (<60 years) and a positive fluorescent anti-nuclear antibody test were associated with a higher probability of SLE conversion (P=0.01 and P<0.001, respectively).ConclusionPrimary AIHA is rare. Regular, vigilant testing for SLE is required in patients initially diagnosed with AIHA.

Potentially Fatal Neutropenia Associated with the Use of Cocaine Adulterated with Levamisole.

AbstractAbstract 3790 Background:Cases of neutropenia associated with the use of cocaine adulterated with levamisole are being increasingly reported and have become a serious public health hazard. As reported by the US Drug Enforcement Administration (DEA) up to 69% of total cocaine seized in the US is adulterated with this veterinary antihelminthic known to cause agranulocytosis in certain susceptible populations. The rationale for selecting levamisole as an adulterant is unclear, but is likely related to the fact that it shares some physico-chemical properties with cocaine and potentiates the activity of dopaminergic (D2) and NMDA receptors in brain thus enhancing its effects. Methods:A case review was performed of adult patients who presented with neutropenia after the use of levamisole adulterated cocaine. Their laboratory results and treatment outcomes were studied to establish an expected course of the illness. Results:Over a one year period, 5 patients (4 female, 1 male) with age range of 45–60 years, presented with neutropenia in the setting of cocaine use. 4 were positive for levimasole in urine (detected by the use of gas chromatography/mass spectrometry analysis within 4–6 hours of presentation). Bone marrow biopsies were performed in 4 cases showed granulocytic hypoplasia with myeloid maturation arrest, lymphocytic hyperplasia and polytypic plasma cells. Antigranulocyte antibodies (AGA) were positive in 3 of the 4 patients tested. One each had positive serology for serum fluorescent antinuclear antibody (FANA), rheumatoid factor (RF) and antineutrophil cytoplasmic antibody (ANCA). Four of the five patients had hepatitis C infection. One patient had marginal zone B cell lymphoma and another was diagnosed with HIV at her first presentation. The median duration of neutropenia was 5–7 days. 2 patients died as a result of their various co-morbidities. Discussion: Use of cocaine adulterated with levamisole can result in profound neutropenia which could be fatal despite aggressive medical therapy. In patients presenting with neutropenia and a history of substance abuse, a high index of suspicion for cocaine adulterated with levamisole is needed and can be confirmed with rapid testing for both substances in patients' urine. Further diagnostic studies including a bone marrow biopsy with characteristic findings as described above and serologic testing for AGA can aid in confirming the diagnosis and ruling out other common causes of neutropenia. The treatment is usually supportive and based on the Infectious Diseases Society of America (IDSA) guidelines for managing neutropenic patients. The role of public health advisories in providing awareness among patients and care givers cannot be overstated, which can lead to early detection and reduced mortality. Disclosures:No relevant conflicts of interest to declare.

Detection of Anti-ENA and anti-dsDNA Antibodies Using Line Immunoassay in Systemic Autoimmune Diseases

Detection of antibodies to extractable nuclear antigens (ENAs) and dsDNA is needed for the diagnosis of and predicting prognosis in systemic autoimmune diseases. Recently introduced line immunoassay (LIA) has the advantage of detecting several autoantibodies simultaneously, and we evaluated its usefulness in the diagnosis of autoimmune diseases in comparison with enzyme-linked immunosorbent assay (ELISA). Samples were collected from 437 patients referred by rheumatologists. FANA (fluorescent antinuclear antibody) test and LIA for the detection of 13 different autoantibodies, including 6 ENAs and dsDNA were performed. LIA-positive samples for ENA or dsDNA antibodies were further tested with ELISA. Final diagnosis was made by rheumatologists according to the diagnostic criteria. Agreement of results between LIA and ELISA was analyzed in 53 selected patients with systemic autoimmune diseases. The LIA detected antibodies to ENA and dsDNA in 118 and 22 patients, respectively, and ELISA detected 70.3% (83/118) and 45.5% (10/22) of LIA positive samples. Especially, 60.2% (71/118) of patients with positive ENA antibody on LIA was diagnosed as systemic autoimmune diseases. Patients having strong FANA titer and homogenous/speckled pattern showed higher prevalence of autoantibodies, but a small proportion of FANA negative patients also showed positive reactivity (LIA 10.8%, ELISA 5.2%). LIA showed a good agreement with ELISA for the anti-ENA antibodies (> or =80%), and a lower agreement for the anti-dsDNA antibody (67.9%). LIA detecting several autoantibodies simultaneously might replace ELISA for anti-ENA antibodies, but not for anti-dsDNA antibodies. When LIA is performed considering clinical manifestations and FANA, it could contribute to the diagnosis of systemic autoimmune disease.

Autoantikörper-Profile bei Kollagenerkrankungen: Eine klinisch-serologische Studie an 250 Patienten aus Tübinger Kliniken

Sera from 250 patients with connective tissue diseases were tested for antinuclear antibodies by immunofluorescence (IFL) and immunodiffusion. In patients with systemic lupus erythematosus (SLE, n = 49), progressive systemic sclerosis (PSS, n = 30) and Sjögren's syndrome (n = 20), IFL showed antinuclear antibodies with a frequency of 70 to 100%. Patients with localized scleroderma (n = 16) and discoid LE (n = 38) had antinuclear antibodies in 31 and 21% of cases, respectively. In patients with vasculitis (n = 32), fluorescent antinuclear antibodies were only rarely detected (0-6%). In the immunodiffusion LE-specific anti-Sm antibodies were demonstrated in 10%, anti-nRNP nRNP antibodies in 20%, and anti-Ro antibodies in 37% of patients with SLE. In Sjögren's syndrome, anti-Ro antibodies were found in 45% and anti-La antibodies in 35% of patients. 57% of patients with PSS had the disease-specific anti-Scl-70 antibody, while only 19% had antinucleolar antibodies as detected by IFL. In patients with localized scleroderma, dermatomyositis (n = 6) or vasculitis, no precipitating antibodies were detectable. The demonstration by immunodiffusion of nuclear antibodies in patients with discoid LE could be connected with a transition to a systemic course of the disease.