6. Brief Resume of the Intended Work s4

Dr. MOUNIKA. K, 12-5-29/4/A, 1. Name of the Candidate and Address VIJAYPURI COLONY, TARNAKA, HYDERABAD- 500017

M S RAMAIAH MEDICAL COLLEGE, 2. Name of the Institution BANGALORE: 560054.

MD in DERMATOLOGY, Course of study and subject 3. VENEREOLOGY & LEPROSY

Date of admission to the course 10/06/2013 4.

AUTOLOGOUS SERUM SKIN TEST AND SKIN PRICK TEST IN CHRONIC 5. Title of the topic IDIOPATHIC URTICARIA- A CROSS SECTIONAL STUDY. 6. Brief resume of the intended work: 6.1. Need for the study:

Chronic urticaria has a profound impact, both physically and psychologically, in most of the patients affecting their day-to-day activities. Despite extensive investigations, a specific cause can be identified only in a few cases. It poses a challenge to the treating physician as well. Simpler procedures like autologous serum skin test (ASST) and skin prick test (SPT) that can be done on an outpatient basis help in identifying the cause of urticaria and its subsequent management.

6.2. Review of literature:

The term urticaria is used to describe a disease that presents with wheals or angioedema or both. It is classified into ordinary, cholinergic, physical and contact urticaria. Ordinary urticaria is acute or chronic or intermittent in nature.1

Urticaria lasting for less than 6 weeks is considered as acute and that occurring on most of the days of a week, for more than 6 weeks is termed chronic urticaria (CU). The term chronic ordinary urticaria is used when predominantly physical, vasculitic and contact urticaria have been excluded. CU affects up to 1% of the general population. There are considerable geographical differences in CU prevalence and markedly higher CU rates of up to 5% in some regions. Up to 70% of patients with CU do not have a well- described cause and hence it is called chronic idiopathic urticaria (CIU). About 40 - 50% of cases classified as idiopathic have an autoimmune basis with circulating mast cell activating factors. Several other factors implicated in provoking CIU are food, food additives, inhalants (pollen, moulds, animal dander and house-dust mites), etc.1,2

The main pathogenic mechanism involved in CIU is mast cell degranulation and histamine release either by mast cell activating factors which are anti IgE receptor antibodies or by triggering agents like food, aero-allergens, etc. This forms the basis for ASST and SPT respectively. Histamine released from the mast cell induces sensory nerve stimulation, vasodilatation and extravasation leading to characteristic clinical symptoms such as pruritus, erythema and edema.2

ASST has a sensitivity of 70% and a specificity of about 80%. The positive results in ASST give an approximate idea of basophil and mast cell histamine releasing propensity of a patient with CIU and correlates with the disease activity. Although basophil histamine release assay is the gold standard for detecting functional autoantibodies in patients with CIU, this bioassay is difficult to standardize because it requires fresh basophils from healthy donors and is time consuming.3

SPT has a definite role in identifying the allergens that could trigger the episode of urticaria and can be an important diagnostic procedure in cases where other investigations are fruitless. In a study from South India on 50 patients with CU, 44% had positive response to SPT towards one or more antigens. Insects and pollen showed maximum number of positive reactions of 24%, followed by 22% for food items.4 In another study from Egypt, out of 69 patients with CU 1.5% showed positive response to SPT.5 A study conducted in Turkey on 259 individuals with CU without respiratory allergy, proved that 27.4% showed immediate cutaneous positivity to SPT. The most common allergens were house dust mite (24.7%), followed by pollen (7.7%), moulds (0.4%) and cockroach (0.8%) respectively.6 Song et al in China, showed through their study that out of 399 patients with CIU, the prevalence of positive ASST was 46.3% and positive SPT to house dust mite was 17.7%.7 In another study of 80 patients from south India with CU, 58.7% proved to be positive for ASST.8.

6.3. Objective of the study:

1) To determine the frequency of ASST and SPT positivity, in patients with CIU.

2) To document the clinical and demographic profile in patients with CIU. 7. Material and methods:

Inclusion criteria

 Patients with symptoms of urticaria lasting for more than 6 weeks in the age group of 18 - 75 years.

Exclusion criteria

1) Patients with the following types of urticaria

 Physical urticaria

 Urticarial vasculitis

 Contact urticaria

 Drug induced urticaria

 Urticarial syndromes

 Urticaria secondary to thyroid disorders

 Patients with urticaria, associated with symptoms of connective tissue disorders eg. photosensitivity and joint pains.

2) Pregnant and lactating women.

7.1. Source of data:

A total of 56 subjects with chronic urticaria attending the dermatology OPD at M. S. Ramaiah hospital will be recruited for the study.

Sample size: The sample size has been estimated to be 56 for statistical significance on the basis of ASST and SPT positivity in similar studies done in India. The sample size for the present study has been estimated with a relative precision of 22% and a desired confidence level of 95%.

7.2. Method of collection:

A total of 56 subjects with chronic idiopathic urticaria attending to the dermatology OPD at M. S. Ramaiah hospital will be recruited for the study. Predesigned proforma including demographics, detailed history, clinical examination and baseline investigations viz. complete blood count, absolute eosinophil count, thyroid function test, routine urine and stool examination will be done for all the subjects recruited. After obtaining the informed consent, ASST and SPT (for standard food and aeroallergens) will be done as per the standard protocol. Patients on antihistamines and immune-suppressants are put off the medication for at least 2 days and 1 month respectively, before the tests. ASST: Autologous serum (0.05ml) is injected intradermally over the flexor aspect of the forearm. Saline is used as negative control and histamine as positive control. The results are read after 30 min. Positive reaction is indicated by a red weal of diameter 1.5mm or more than that of the control. SPT: A drop of allergen is placed on the flexor aspect of forearm. The solution is allowed to enter the skin using a needle. Saline is used as the negative control and histamine as the positive control. Positive skin prick test is a wheal of 3mm or more than the control developing after 15 min.

Type of study: Cross-sectional study design.

Statistical analysis: Descriptive statistics of ASST and SPT will be analysed and presented in terms of percentage and its 95% confidence interval will be determined. 7.3. Does the study require any investigations or interventions to be conducted on patients or other humans or animals?

Yes, as detailed above (ASST, SPT and baseline investigations).

7.4. Has ethical clearance been obtained from your institution in case of 7.3?

Reference: 1) Grattan C.E.H. and Black A.K. Urticaria and mastocytosis. In: Rook’s textbook of dermatology. Eds: Burns T, Breathnach S, Cox N, Griffiths C, 8th edn, Wiley- Blackwell 2010; 22.1- 22.35. 2) Maurer M. Chronic urticaria. In: Urticaria and Angioedema. Eds: Zuberbier T, Grattan C, Maurer M, Springer Verlag Berlin 2010; 45- 56 3) Haldar B, Ghosh S, Haldar S. Cutaneous vascular responses. In: IADVL Textbook of Dermatology. Eds: Valia RG, Valia AR, 3rd edn, Bhalani publishing house- Mumbai 2008; 642-680. 4) Nath A, Balaji A, Thappa DM. Prick testing in chronic idiopathic urticaria: A report from a tertiary care centre in south India. The Internet Journal of Dermatol, 2007; 6 5) Azim ZA, El Mongy S, Salem H. Autologous serum skin test in chronic idiopathic urticaria: a comparative study in patients with positive versus negative test. J Egypt Women Dermatol Soc 2010; 7: 129- 133. 6) Caliskaner Z, Ozturk S, Turam M, Karayvaz M. Skin test positivity to aeroallergens in the patients with chronic urticaria without allergic respiratory disease. J Invest Allergol Clin Immunol 2004; Vol.14 (1): 50-54 7) Song Z, Zhai Z, Zhong H, Zhou Z, Cheng W. Evaluation of autologous serum skin test and skin prick test reactivity to house dust mite in patients with chronic spontaneous urticaria. PLOS ONE 2013, 8(5): e64142. Accessed on 10th oct 2013. 8) Krupashankar DS, Shashikala K, Madala R. Clinical and investigative assessment of patients with positive versus negative autologous serum skin test. Indian Journal Dermatol 2012; 57(6): 434-438 9. Signature of the Candidate

Remarks of the Guide Nearly half the cases of chronic urticaria have autoimmune basis and a number of foods and aero allergens can trigger urticaria. 10 The present study is undertaken . to make the candidate well versed with the techniques such as ASST and SPT that help in identifying the cause and in managing urticaria effectively.

11.1.Name and designation of the Dr. K.N. SHIVASWAMY, Guide ASSOCIATE PROFESSOR, Dept. of DERMATOLOGY, M S RAMAIAH MEDICAL COLLEGE.

11.2. Signature of the Guide

11 . 11.3. Name and designation of the Dr. A.L. SHYAM PRASAD Head of the Department PROFESSOR & HOD Dept. of DERMATOLOGY, M S RAMAIAH MEDICAL COLLEGE.

11.4. Signature of the Head of the Department 12.1. Remarks of the Principal

12.2. Signature of the Principal