INTRODUCTION The term chronic spontaneous urticaria (CSU) is used to describe those cases in which the cause could not be determined despite of intensive clinical and laboratory investigations. Autoimmune mechanisms have been proposed to cause some cases of CSU. This was supported by the observation that an intradermal injection of autologous serum (autologous serum skin test) elicited immediate wheal and are response in 60% of patients with CSU (1).Later IgG autoantibodies directed against IgE or FCERI receptor on IgE were demonstrated and were found to be the cause of autoimmune Urticaria (2). The autoimmune process in CSU overlaps with many other autoimmune diseases, most common amongst them is the autoimmune thyroid disease (3). The incidence of thyroid autoantibodies in patients with CU ranges from 6.5% - 57% (4, 5). Total IgE has been found to be raised in patients with CU. This is because of polyclonal activation of B cells in CU (6).Thus, autoimmune markers like antinuclear antibodies (ANA), rheumatoid factor (RF), anti- thyroid peroxidase antibodies (anti-TPO Ab), autologous serum skin test (ASST) and total IgE are important investigations in CSU. Characterization of inammatory response - erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP) are essential for an insight into the pathophysiology of the disease as well as its activity, severity and diagnosis/management of infections and autoimmune diseases in the course of chronic Urticaria (7). Infections can cause urticaria by inducing molecular mimicry, hence identication and management of infections in patients of CU is essential (8). MATERIALS AND METHODS We retrospectively evaluated 134 patients of chronic urticaria seen in allergy clinic of Department of Dermatology, Venereology and Leprosy at AVBIMS Dr. Ram Manohar Lohia Hospital, after taking approval from recent 2 years span instituitional ethical board. Patients of acute urticaria (duration of urticaria<6 weeks), physical Urticaria (excluded with proper history), urticarial vasculitis, children less than 12 years, pregnant and lactating women were excluded. Data were collected regarding, age, sex, disease duration, severity and laboratory parameters. We used urticaria activity score (UAS) to assess severity of the disease Autologus serum (9). skin test(ASST) done for each patients by injecting intradermaly of 0.1 ml each of autologous serum, saline (negative control) on the volar aspect of left forearm with a gap of 5 cm between each injection site. After 30 minutes the wheal formed at each injection site were measured at two perpendicular diameters (d1, d2) and the average of the two was calculated. ASST was considered to be positive if serum- induced wheal had a diameter (average of d 1 and d 2) of ≥1.5 mm as compared to the saline-induced wheal at 30 minutes (10). Various serologic autoimmune and inammatory markers including, anti- assessed by different methods nuclear antibodies (ANA), rheumatoid factor (RF), thyroid autoantibodies-thyroperoxidase (anti- TPO<50IU/ml), serum total IgE (female<175, male<250IU/ml) and C-reactive protein (CRP) assessed by ELISA. Thyroid function test (TFT) by chemiluminesense (Vitros Eci, and jhonson and jhonson) anti-streptolysin antibodies (ASO) by latex agglutination method . Comple te haemogram and e r y th rocy te sedimentation (ESR), routine and microscopic examination of urine and stool examination for ova and cyst were done for each participant. STATISTICAL ANALYSIS For demographic and other clinical variables we use descriptive statistics, using Mean ± Standard Deviation and percentage (frequency). We compared between all clinical with laboratory variables by using ANOVA. Pearson correlation was used to nd correlation of these lab and clinical variables. A p value of <0.05 was considered as statically signicant. We used SPSS soft version 20.0. RESULTS Of the 134 patients with chronic spontaneous urticaria 92(68.7%) were female, 42(31.3%) male with the average age of 35 year (14yrs-72yrs). The duration of the onset of disease was average 38 months (2 - 360months). Urticaria activity score was found to be of moderate grade among 84(62.7 %), severe grade 31(23.1 %) and mild grade 19(4.2 %). Autologus serum skin test (ASST) was positive in 40(29.9%). Among 40, TO EVALUATE THE ASSOCIATION BETWEEN CLINICAL PARAMETERS OF CHRONIC URTICARIA AND VARIOUS BIOMARKERS Original Research Paper Dr Seema Rani* Associate Professor, Department of Dermatology, ABVIMS, DR RMLH, New Delhi *Corresponding Author Dermatology Introduction: Causes of chronic urticaria (CU) remain obscure. Laboratory parameters or biomarkers can be a predictor of duration and severity of Urticaria. Objective: The aim of this study was to evaluate the association between clinical parameters of chronic urticaria and various biomarkers. Methods: A retrospective cross-sectional data of 134 patients of chronic urticaria seen in allergy-clinic, during recent 2 years span were collected. Demographic details, duration of the disease, urticaria activity score (UAS), Autologus serum skin test (ASST) and various autoimmune and inammatory laboratory parameters were included. Results: We found disease activity (UAS) was signicantly associated with biomarkers, ASST (.044), CRP (.025) and ANA (.000). ANA positivity was signicantly (.000) associated with duration of the disease. Conclusions: The present study found association of chronic urticaria with inammatory and autoimmune markers; hence it is important to monitor certain laboratory testings like, CRP, ESR, ANA, ASST, Thyroid auto antibodies, IgE and routine blood count to predict the disease duration, severity and to manage patients appropriately. ABSTRACT KEYWORDS : Urticaria; biomarkers; Autoimmunity; Inammatory Dr Niharika Dixit Senior Resident, Department of Dermatology, ABVIMS, DR RMLH, New Delhi. Dr Devika choudhry Post graduate student, Department of Dermatology, ABVIMS, DR RMLH,New Delhi. VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra 44 X GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS Dr P. K. Sharma Professor, Department of Dermatology, ABVIMS, DR RMLH, New Delhi 26(65%) were female and 14(35%) were male. Anti-nuclear antibodies and rheumatoid factors were found to be positive in 20(14.9%) of patients. Both ANA and RF were raised in only 3 patients (2.2%). Out of 20 rheumatoid factor and ANA positive patients, 12(60%) were female and 8(40%) male. ANA and ASST were positive in 10 (7.46%) cases. 31(23.5%) had risen anti thyroid antibodies. Serum IgE was signicantly raised in 82(61.2%). Laboratory inammatory markers ASO and CRP were positive in 11(8.2%) and 49 (36.6%) respectively. Routine stool and urine samples were showed 13(9.7%) and 31(23.1%) positive for cyst of giardia and bacteria respectively. ESR was raised among 32(25%) patients as shown in table1, 2. There were no signicant difference of all clinical and lab parameters in both sexes except ESR in female (p=.007), comparison to male. We found positive association of age with duration (p=.000), serum IgE (p=.025) and ESR (.044). The study showed positive association of CRP with UAS (.025) and raised count of total leucocytes (.025). Absolute eosinophil counts (AEC) was associated with raised TLC and UAS with statistical signicant p value of .025 and .043 respectively. Raised ESR associated with ANA, Anti-TPO and positive stool test for giardiasis with signicant p value.026, .024 and .027 respectively. All CU patients with RF positive were associated with raised serum IgE (.020) ANA positivity was signicantly (.000) associated with duration of the disease, raised ESR (0.026) and UAS (0.000). Positive result of ASST was signicantly correlated with UAS (.044) as shown in table 3. Angioedema was found in only 4(3%) person. DISCUSSION The present study has shown 68.7% female preponderance similar to previous studies (11). The mean age of the patients were 35.45 years which was comparable to the study done by George et al (13).Average duration of chronic urticaria was 38 months and CU patients with ANA positivity had prolonged duration (11). We found, elderly patients had prolonged disease-duration (.000) with raised value of ESR (.040) and serum IgE (.025). Although measuring ANA serves as a nonspecic marker of systemic autoimmunity, its relationship with CU is poorly understood. Nonetheless, positive ANA has been found to have some correlation with CIU severity and was strongly associated with refractoriness to antihistamines (14). was associated Whereas in other study CU duration clinical parameters such as severity and angioedema, and presence of both autologous serum test and anti-thyroid antibodies (15). In our study disease duration was associated with age, CRP, ANA and ASST positivity. ASST was found to be positive in 40 patients (29.9%), these were associated with moderate to severe grade of urticaria (UAS). Some studies also showed severe clinical features in ASST positive CU than ASST negative(16), in contrast to the other study which did not found such association (17). Similar to most of the previous studies, our study was found positive correlation between CRP and severity of Urticaria (17, 18).This indicates that CRP levels reect activity of disease and it may serve as a biomarker to monitor CSU patients. CRP positive individual also had raised total leukocytes counts (TLC). We found association of raised serum IgE with positive RF. RF were positive in 20(14.9%) patients all had raised serum IgE level. Earlier studies also found high titres of IgE in serum of rheumatoid arthritis (RA) (19, 20)patients but no increased prevalence of atopy (21, 22) rather decreased prevalence (23). De Clerck et al. found elevated IgE levels and IgE circulating immune complex in RA patients more frequently than in patients with allergic asthma and good correlation between skin IgE deposition and extra articular manifestations of RA. In our studies we did not nd any clinical severity in RF positive CU patients with raised serum IgE. We also did not found any correlation of thyroid autoantibodies to sex, duration, severity, ASST, ANA positivity in CU. Elevated ESR was seen in thyroid auto-antibodies positive patients (p=.024) similar to result found in other study (24), ANA positive, female and elderly individuals and patients associated with positive stool test for ova and cyst . Raised AEC were found to be associated with raised TLC and CU severity. CONCLUSIONS In our study we found, chronic urticaria was seen more commonly in female. Disease duration was prolonged in elderly and patients with autoimmunity. Disease severity was found to be associated with inammatory marker-CRP positivity, peripheral eosinophilia and ANA, ASST positivity. Hence, it is important to monitor certain laboratory testings like, CRP, ESR, ANA, ASST, Thyroid auto antibodies, IgE and routine blood count to predict the disease duration and severity and to manage patients appropriately. The limitation was that we have not covered the therapeutic part/response in our patients, no comparison with healthy control and also the sample size was not adequate to derive any nal conclusion. Acknowledgement: For statistical analysis.Dr Triptish Bhatia, Ph.D. Senior Research Scientist, Indo-US Projects, Dept. of Psychiatry, Center of Excellence in Mental Health, PGIMER, Dr RMLH, New Delhi, India. Table1. Showing demographic and clinical prole Table 2. Percentage of patients with positive inammatory and autoimmune markers. ESR- Erythrocyte sedimentation rate, CRP-C-reactive protein, ASO- Antistreptolysin O, AEC- Absolute eosinophil count, Total leukocyte count ANA- Antinuclear antibodies, Anti-TPO- Anti thyroid peroxidise, ASST- Autologus serum skin test, RF- Rheumatoid factor VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra Sex Males Females Number of patients (%) (n=134) 42 (31.3%) 92 (68.7%) Mean±SD 52.17+83.46 31.20+41.75 Age (years) Range 14-72 35.45±11.94 Duration(months) Range 2-360 37.77±58.61 Severity of urticaria (UAS7) Mild Moderate Severe 19 (14.2%) 84 (62.2%) 31 (23.1%) 27.54±8.364 Inammatory markers Positive (No. of patients, %) n=134 Autoimmune markers Positive (No. of patients, %) n=134 ESR 32 (25%) ANA 20 (14.9%) CRP 49 (36.6%) Anti- TPO Antibodies 31 (23.5%) ASO 11 (8.2%) ASST 40 (29.9%) AEC 24 (17.9%) RF 20 (14.9%) TLC 7 (5.2%) S. IgE 82 (61.2%) Table 3. Signicant correlation between various clinical and laboratory parameters. Inammatory markers with demographic and autoimmune parameters *P value Autoimmune markers with demographic and inammatory parameters *P value Demographic with autoimmune and inammatory parameters *P value ESR Stool for ova and cyst 0.027 ANA Duration 0.000 Duration ANA 0.000 X 45GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS *p value signicant below 0.05 level, ESR- erythrocyte sedimentation rate, CRP- C-reactive protein, UAS- Urticaria activity score, TLC- Total leukocyte count, AEC- Absolute eosinophil count, ANA-Antinuclear antibodies, ASST- Autologus serum skin test, RF- Rheumatoid factor REFERENCES 1. Sabron RA, GrattanCE,Francis DM, Barr RM, Kobza Black A, Greaves MW. The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria. Br Dermatol 1999; 140:446-52. 2. Hide M, Francis DM, Grattan CEH, Hakimi J, Kochan JP, Greaves MW. Auto antibodies against the high afnity IgE receptor as a cause of histamine release in chronic urticaria. N Eng J Med 1993; 328:1599-604. 3. Conno Cohen R, Chodick G, Shalev V et al. Chronic urticaria and autoimmunity: Associations found in a large population study. J Allergy Clin Immunol. 2012; 129(5):1307-13. 4. Atta AM, RodriguesMZA, Sousa CP, Medeiros Junior M, Sousa-Atta MLB. Autoantibodies production in chronic idiopathic urticaria is not associated with Helicobacter pylori infection. Braz J Med Biol Res 2004;37:13-7. 5. Aamir IS, Tauheed S, Majid F, Atif A. Frequency of autoimmunethyroid disease in chronic urticaria. J Coll Physicians Surg Pak 2010;20:158-61. 6. Kessel A, Helou W,Bamberger E, Sabo E, Nusem D, Panassof J, Toubi E. Elevated Serum Total IgE- A Potential Marker for Severe Chronic Urticaria. Int Arch Allergy Immunol 2010; 153:288-93. 7. Kasperska-ZajacA, Acute-phase response in chronic urticaria. J Eur Acad Dermatol Venereol. 2012; 26:665-72. 8. Wedi B, Raap U, Weickzorek D, Kaap A.Urticaria and infections. Allergy, Asthma &Clinical Immunology. 2009; 5:10. 9. GodseKV.Urticariameter.IndianJDermatol2012; 57:410-1. 10. Ghose SK, Ghosh S. Autologous Seum Skin Test. Indian Journal of Dermatology. 2009;54(1):86-87. 11. Irinyi B, Sze ĺ es G, Gyimesi E, et al. Clinical and laboratory examinations in the subgroups of chronic urticaria. Int Arch Allergy Immunol 144:217–225, 2007. 12. Magen E, Waitman DA, Dickstein Y, Davidovich V, Kahan NR. Clinical- laboratory characteristics of ANA-positive chronic idiopathic urticaria. Allergy Asthma Proc.2015 Mar-Apr; 36(2):138-44. 13. George M, Ba lachandran C , Prabhu S . Chron ic id iopa th ic urticaria:Comparison of clinical features with positive autologus serum skin test.Indian J Dermatol Venereol Leprol 2008;74:105-8 14. Viswanathan RK, Biagtan MJ, and Mathur SK. The role of autoimmune testing in chronic idiopathic urticaria. Ann Allergy Asthma Immunol 108:337–341.e1, 2012 15. Toubi E. Kessel A. Avshovich N. Bamberger E. Sabo E. Nusem D. Panasoff J.Clinical and laboratory parameters in predicting chronic urticaria duration: a prospective study of 139 patients.Allergy.2004 Aug; 59(8):869-73. 16. Caproni M, Volpi W, Giomi B, et al. Chronic idiopathic and chronic autoimmune urticaria: clinical and immunopathological features of 68 subjects. Acta Derm Vererol 2004; 84:288–90. 17. Rabelo-Filardi R.Daltro-Oliveira R.Campos R.A. Parameters associated with chronic spontaneous urticaria duration and severity: A Systematic Review. Int Arch Allergy Immunol 2013; 161:197-204. 18. Kolkhir P, Altrichter S, Hawro T, Maurer M. C-reactive protein is linked to disease activity, impact, and response to treatment in patients with chronic spontaneous urticaria. Allergy.2018 Apr; 73(4):940-48. 19. Grennan DM, Palmer DG. Serum IgE concentration in rheumatoid arthritis: lack of correlation with gold toxicity. Br Med J. 1979;2:1477–8. 20. Hunder GG, Gleich GJ. Immunoglobulin E (IgE) levels in serum and synovial uid in rheumatoid arthritis. Arthritis Rheum. 1974;17:955–63. 21. O'Driscoll BR, Milburn HJ, Kemeny DM, Cochrane GM, Panayi GS. Atopy and rheumatoid arthritis. Clin Allergy. 1985;15:547–53. 22. Hasan WU, Keaney NP, Holland CD, Kelly CA. Bronchial reactivity and airow obstruction in rheumatoid arthritis. Ann Rheum Dis. 1994;53:511–4. 23. Allanore Y, Hilliquin P, Coste Renoux M, Menkès CJ. Decreased prevalence of atopy in rheumatoid arthritis. Lancet. 1998;351:497. 24. Kumutnart Chanprapaph , Wimolsiri Iamsumang,Penpun Wattanakrai, and Vasanop Vachiramon. Thyroid Autoimmunity and Autoimmunity in Chronic Spontaneous Urticaria Linked to Disease Severity, TherapeuticResponse, and Time to Remission in Patients with Chronic Spontaneous Urticaria. Hindawi BioMed Research International Volume 2018, 13 pages. VOLUME-8, ISSUE-11, NOVEMBER-2019 • PRINT ISSN No. 2277 - 8160 • DOI : 10.36106/gjra ESR Age 0.044 ANA UAS 0.000 Age ESR 0.044 ESR ANA 0.026 ANA ESR 0.026 Age Duration 0.000 ESR Anti- TPO antibodies 0.024 Anti TPO antibod-ies ESR 0.024 Age S. IgE 0.025 ESR Sex (female) 0.007 ASST UAS 0.044 Sex ESR 0.007 CRP UAS 0.025 RF Serum IgE 0.020 CRP TLC 0.025 AEC UAS 0.043 AEC TLC 0.025 46 X GJRA - GLOBAL JOURNAL FOR RESEARCH ANALYSIS