Diagnostic testing and ominous causes of headache
Stephen D. Silberstein, Richard B. Upton, Peter J. Goadsby in Headache in Clinical Practice, 2018
Refractory headache patients who attend tertiary referral centres usually undergo a greater number of studies than do those patients seen in specialists’ or primary care physicians’ offices. Since secondary causes of headache frequently are not apparent on physical examination, laboratory tests are sometimes performed on the initial visit to facilitate their diagnosis. A complete blood count and differential may rule out anaemia or infection. The antinuclear antibody test screens for autoimmune conditions. An erythrocyte sedimentation rate not only acts as a screen for serious diseases, such as a malignancy or collagen vascular disease, but can also establish the diagnosis of temporal arteritis, a cause of headache in the elderly. Thyroid function studies are performed to rule out thyroid disease such as thyrotoxicosis, a condition that may exacerbate headache and is a relative contraindication to ergot administration. Unexpected or overused medication that has a direct impact on headache and its treatment can be identified by a drug screen and toxicology studies. Specific studies (such as electrolytes and liver or kidney function studies) may be needed before starting drug treatment.
Rheumatologic diseases and antiphospholipid syndrome
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Diagnosis depends upon characteristic clinical manifestations together with confirmation by typical laboratory abnormalities (1–4,93). The antinuclear antibody (ANA) test is positive in essentially all SLE patients. However, it also occurs frequently in other CTD. The ANA has greater diagnostic import when either absent (tending to exclude SLE) or when present in high titers, especially with homogeneous or peripheral-staining nuclear patterns (typical of SLE). An isolated low-titer ANA lacks association with SLE or adverse pregnancy outcome, compared with high-titer ANA or the more specific antibodies that correlate with this disorder. The specific and confirmatory immunologic abnormalities of SLE include anti-native (double-stranded) DNA (nDNA) or anti-Smith (Sm) antibody. Positive lupus erythematosus (LE) cell preparation, a test that is rarely performed today, or chronic (at least 6 months) biologic false-positive test for syphilis supports, but does not confirm the diagnosis, since these serologic findings are typical but are not specific for SLE (1).
Analyzing Complex Polygenic Traits
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
Finally, both disease and genetic heterogeneity are other confounding factors that often affect the results of linkage studies. Disease heterogeneity is best illustrated in SLE in which patients may present with several combinations of symptoms (rash, arthritis, glomerulonephritis, central nervous system disease, etc) and serological findings (antibodies against dsDNA, Ro, La, etc) that usually cluster in mild versus severe forms of the disease. While both forms of SLE may represent the ends of the same disease spectrum, it is also possible that they constitute distinct disease etiologies sharing several common genetic susceptibility factors but are differentiated by specific disease-associated alleles. Dissection of the original disease into intermediate phenotypes that are used in linkage studies could overcome this problem. Similarly, healthy members of SLE multiplex families are known to be more frequently positive for the presence of antinuclear antibodies than controls. While a linkage study based on the presence or absence of disease would weaken the probability of finding genes associated with antinuclear antibody production, the use of more specific component phenotypes may enhance the power of the analysis. Finally, genetic heterogeneity indicates that multiple combinations of genes within the genome may result in identical disease phenotypes, a common feature of many genetic systems that can clearly affect the power of linkage analysis in outbred populations.
Hereditary afibrinogenemia and pulmonary-renal hydralazine-induced vasculitis
Published in Baylor University Medical Center Proceedings, 2019
Ginger Tsai-Nguyen, Ariel M. Modrykamien, Arthur Bredeweg
His blood hemoglobin level was 9.0 g/day; hematocrit, 27%; serum creatinine, 2.16 mg/dL; erythrocyte sedimentation rate, 87 mm/h; C-reactive protein, 10.0 mg/dL; and fibrinogen, 59 mg/dL. Autoimmune workup revealed antinuclear antibody positivity, with a dilution of 1:160 and a nucleolar pattern and 1:640 with a homogenous pattern. His P-antineutrophil cytoplasmic antibodies (ANCA) were positive at 1:2560, and his histone antibodies were 4.7 units. His anti-double-stranded DNA was positive at 1:40, and proteinase-3 antibodies and myeloperoxidase (MPO) were both positive. His urinalysis showed 2+ protein, 3+ blood, and 50 to 100 red blood cells. Significant cuts of the chest computed tomography scan are shown in Figure 1. Based on the aforementioned findings, a renal biopsy was performed, which showed focal necrotizing pauci-immune glomerulonephritis, severe interstitial fibrosis-tubular atrophy (70%–80%), and changes of acute tubular injury (Figure 2). The patient was diagnosed with hydralazine-induced ANCA vasculitis with pulmonary-renal syndrome. He was initially treated with cryoprecipitate to increase fibrinogen levels to >100 mg/dL; hydralazine was stopped. He was started on prednisone 60 mg daily, with subsequent improvement of dyspnea and oxygenation. He was ultimately tapered off of steroids and completed a course of rituximab with return of his kidney function to baseline. He has been in remission for 3 months after his initial presentation.
Post-marketing safety surveillance of erenumab: new insight from Eudravigilance
Published in Expert Opinion on Drug Safety, 2022
Antinuclear antibody, C-reactive protein increased, and liver function test increased were identified as signals of disproportional reporting. The antinuclear antibody test is used in clinics to support the diagnosing of autoimmune diseases. Previous studies have described, in a clinical setting, the increase of antinuclear antibody levels in individuals with migraines. Therefore, we cannot exclude that this disproportionality signal is confounded by indication or rather that erenumab is used for migraines and consequently associated with increased biomarkers in migraines [29]. Similarly, positive C-reactive protein is increased in patients with migraines with complex clinical features such as those leading to treatment-resistant migraines requiring second-line treatment such as erenumab [30]. A recent update of the safety information on erenumab highlighted the occurrence of liver injury and increased biomarkers of liver injury [31]. However, in many cases, there was limited information for a proper assessment of the individual causality. This disproportionality signal merit further investigation as pre- and post-marketing clinical trials investigating the safety of erenumab excluded individuals with preexisting liver disorders [32,33]. However, it should also be mentioned that erenumab is not metabolized by the liver and, therefore, the probability of developing erenumab-induced liver injury are quite limited [34].
Intestinal angioedema caused by an acquired C1 esterase inhibitor deficiency associated with underlying splenic marginal zone lymphoma
Published in Baylor University Medical Center Proceedings, 2021
Thanita Thongtan, Anasua Deb, Genanew Bedanie, Mohamed Elmassry, Matthew Soape, Kenneth Nugent
Contrast-enhanced computed tomography (CT) of the abdomen and pelvis showed splenomegaly (16.1 cm) with splenic varices and bowel wall thickening with mucosal enhancement suggestive of enteritis (Figure 1). Small bowel enteroscopy showed jejunal narrowing at 70 cm distal to the pylorus without signs of inflammation; the biopsy result was normal. Colonoscopy was unremarkable. The FibroScan score was 7.7 kPa. A complete blood count showed pancytopenia, with white blood cells 2.89 k/µL, hemoglobin 9.3 g/dL, mean corpuscular volume 84.3 fL, and platelet count 96 k/µL. A peripheral blood smear showed pancytopenia with no atypical cells. The complement component 4 level was low at <6 mg/dL (normal 10–40 mg/dL), C1-INH protein level was low at 4 mg/dL (normal 21–39 mg/dL), and C1-INH protein function was low at 18% (normal ≥68%). An antinuclear antibody test was negative. Peripheral blood flow cytometry revealed a small population (0.1%) of monoclonal B cells with nonchronic lymphocytic lymphoma type, with no evidence of an aberrant T-cell process or increased blasts. Bone marrow biopsy revealed a hypercellular marrow (60%) with megakaryocytic hyperplasia but no evidence of B-cell lymphoma involvement. Fluorescence in situ hybridization was negative for abnormalities of chromosomes 3, 7, 11, 18, rearrangements of BCL6, MALT1, or t(11;14) translocation. The cytogenetic result was normal (46, XX).
Related Knowledge Centers
- Autoantibody
- Autoimmunity
- Cell Nucleus
- Antigen
- Anti-Ssa/Ro Autoantibodies
- Sjögren Syndrome
- Anti-Nrnp
- Anti-Scl-70 Antibodies
- Anti-Dsdna Antibodies
- Anti-Histone Antibodies