ABSTRACT
Background: The aim of the present study is to evaluate the efficacy of Safoof-e-ajwain in the management of shara (Urticaria).
Materials & Methods: All the patients received same dosage of Unani drug for decided period. 37 patients were enrolled in the study (26 Males and 11 Females). 30 patients (19 males & 11 females) completed the study & 7 patients were lost to follow-up. Thirty patients, aged between 20 to 60 years, of either sex (who attended the outpatient department, with clinical evidence of Shara (Urticaria) were included in the study. BSL-Random was done on first day of visit before starting the medicine. The cases received Safoof-e-ajwain 10.5 grams orally for 45 days. The patients were followed every 15 days for the period of 45 days. Clinical evaluations were done. Statistical analysis was done.
Results: The average UAS score is significantly higher at visit 1 compared to visit 2 UAS score (P-value<0.05). The average UAS score is significantly higher at visit 1 compared to visit 3 UAS score (P-value<0.001). The mean % reduction in UAS score at visit 3 was 25.61% compared to the UAS score at visit 1. The average UAS score is significantly higher at visit 1 compared to visit 4 UAS score (P-value<0.001). The mean % reduction in UAS score at visit 4 was 35.96% compared to the UAS score at visit 1. Conclusion: Shara (Urticaria) occurred in different religions of people mostly in Upper middle class. Majority of thin patients followed by fatty & broad type of physique had Shara (Urticaria). Males & females of 3rd decade of life having prevalence of allergy was present in majority of cases. In patients of Shara (Urticaria) poor appetite was present. Urticarial patients had no addiction except very few.
Keywords: Urticaria, Safoof-e-Ajwain, Management, Shara, Allergy.

INTRODUCTION

Urticaria is one of the most frequent skin diseases. It is characterized by pruritic wheal & flare-type skin reactions with or without angioedema that usually persist for <24 hours. In some patients, only angioedema is present (Maurer et al., 2011). Urticaria is a heterogeneous group of diseases that result from large variety of underlying causes, are elicited by a great diversity of factors & present clinically in a highly variable way. Urticaria has profound impact on quality of life & effective treatment is, therefore, required (Zuberbeir et al., 2009). Urticaria is a common reaction pattern in which pink, itchy or ‘burning’ swellings (wheals) can occur anywhere on the body. Individual wheals do not last longer than 24 hours, but new ones may continue to appear for days, months or even years (Richard et al. 2008). Persons in any age group may experience acute or chronic urticaria and/or angioedema, these lesions increase in frequency after adolescence, with the highest incidence occurring in persons in the third decade of life; indeed, one survey of college students indicated that 15-20% had experienced a pruritic wheal reaction (Harrisson et al., 2012). Any part of the body may be affected. Trunk is involved more commonly than extremities or face, but in a patient, it is common to obtain a history of involvement of various body regions. Mucosae may also become swollen, lips being the commonest region, being affected (Khopkar2009). Chronic urticaria is more common in adults, affecting women (75% of cases) more often than men (Goldman et al., 2007). Urticaria (from the Latin word Urtica, (to burn) or hives), are, a kind of skin rash notable for dark red, raised, itchy bumps7There was bimodal age distribution among patients with peaks at birth to 9 years & 30-40 years (Klaus et al., 2008). Urticaria is one of the most common dermatologic disease with many different clinical manifestations (Tony Burns, 2008). Allergic diseases are common and increasing cause of illness, affecting between 15% and 20% of the population at some time. They comprise a range of disorders from mild to life-threatening, and affect many organs (Marshal, 2010). In around 30% patients of urticaria, attacks often recur for months or years (Clive. 2002). Urticaria and angioedema may coexist in 50% of cases. Systemic symptoms like malaise, abdominal pain, dizziness, arthralgia, hoarseness, syncope or even anaphylaxis may sometimes be associated with Urticaria and angioedema (Vibhu, 2012). Urticaria has been recognized since the days of Hippocrates. The term dates back to the 18th century, when the stinging and burning was likened to the sting of a nettle (Urticadioica).The changing opinions on the pathogenesis and management of urticaria provide a fascinating reflection of the changing fashions in medical thought (Rook, 1974; Czarnetki, 1989). Shaikh Ibn-e-Sina mentions about Shara as “Small and flat topped eruptions resembling vesicles (nifatat) ,reddish in colour , with severe itching and pricking sensation and most often arise suddenly in the whole body and sometimes a fluid oozes from these busoor” (Ibn-e-Sina 2010). According to Ismail Jurjani “vapours of dam-e-merari (bilious blood) &balgham e boraqi (acidic phlegm) coming outwards spontaneously, produce Shara” (Jurjani, 2010). Two causes of shara mentioned in Kamil-us-Sana’a 1. Blood in which safra has mixed in abnormal quantity. 2. Mixing of Balgham-e-Shor (saline Phlegm) in dam-e-raqeeq (Thin blood) (Majoosi, 2010). AbulHasan Ahmed bin RabbanTabri (994 B.C.) writes in his book ‘Moalijat- e- Buqratiya’ that “when condition of urticaria is ignored to manage, it creates, disorders, affecting skin & its pores, leading to weaknesses of nerves that cause accumulation of pathogenic material at sites. As a result, skin diseases like, boils, carbuncle, pustular conditions & pathogenesis in underlying muscles occur. All these changes consequently appear as loss of function of organs”(Tabri,1997).

MATERIALS AND METHODS

Aim of the study was to evaluate clinical efficacy of Unani Formulation in the management of Shara (Urticaria) on Unani & Modern Scientific Parameters. This was a Prospective Open label, Clinical study approved by the Institutional Ethical Committee. Thirty patients, aged between 20 and 60 years, of either sex (who attended the outpatient department with clinical evidence of Shara (Urticaria) were included in the study. A written informed consent document was obtained from all these patients. Prior to the study, all patients had clinical symptoms of Shara. These patients had clinical evidence of Shara. Exclusion criteria were Patients having signs& symptoms of complicated Shara (Urticaria). Patients with secondary infection. Pregnant & lactating women. Patients having diabetes, renal/hepatic disorders, mental retardation, immunological disorders. Immunocompromised persons. Investigator’s decision. Withdrawal criteria were Loss to follow up with gap of more than 7 days in treatment, Any adverse effect, Disease progression.
Parameters of Evaluation
1. General examination—–History, symptoms, signs.
2. Local examination.
3. Following investigations will be carried out in the patients before the treatment.
BSL-Random
The patients will be assessed clinically through Urticaria Assesment Score (UAS). It is internationally used method to measure efficacy of test drug in clinical study for Urticaria.
Assessment of Mizaj (Temperament): In each selected patient, assessment of Mizaj (Temperament) will be done on the basis of AJNAS- E- ASHRA & other parameters mentioned in Classical Unani Literature. In Unani System of Medicine Mizaj is an important evaluation parameter. Relation between Mizaj type & occurrence of URTICARIA (SHARA) would be studied.
The Test group received Safoof-e-Ajwain powder (with water) orally once daily for a period of 45 days.
The patients were followed up for 45 days and symptomatic evaluation was recorded after the completion of 15 days. The outcome measure for efficacy was a decrease in the Urticaria Activity Score at the end of 45 days.

RESULTS

Table 1-6. Compounds 1-4 isolated from methanolic extract of seeds of Lens culinaris Medik. Click here to view full image

Table 1. Comments: 1. Of 30 cases studied, 12 cases (40.0%) had age less than 30years; 11cases (36.7%) had age between 30 to 39 years; 7 cases (23.3%) had age more than or equal to 40 years.
2. The mean ± SD, (Min – Max) of age of the group was 32.8 ± 9.4years (Min = 20 years, Max = 55 years).
Table 2. Comments: 1. Of 30 cases studied, 19 cases (63.3%) were males; 11 cases (36.7%) were females.
2. Majority of the cases studied were males
Table 3. Comments: 1. Of 30 cases studied, 27 cases (90.0%) were Muslims; 3 (10.0%) were Hindus
2. Majority of the cases studied had Muslim religion.
Table 4. Comments: 1. Of 30 cases studied, 19 cases (63.3%) were married; 11 (36.7%) were unmarried
2. Majority of the cases studied were married.
Table 5. Comments: 1. Of 30 cases studied, 6 cases (20.0%) were Housewives, 10 (33.3%) were Students, 8 (26.7%) were doing service and 6 (20.0%) were self employed.
2. Majority of the cases studied were students.
Table 6. Comments: 1. Of 30 cases studied, 13 cases (43.3%) had Safravi Mizaj. 12 cases (40.0%) had balghami Mizaj
5 cases (16.7%) had Damvi Mizaj
2. Majority of the cases studied had Safravi Mizaj.
3. Patient of Shara, with Saudavi Mizaj, not found.

Table 7-12. Compounds 1-4 isolated from methanolic extract of seeds of Lens culinaris Medik. Click here to view full image

Table 7. Comments: 1. Of 30 cases studied, 21 cases (70.0%) had allergy and 9 (30.0%) did not have any allergy.
2. Large majority of the cases studied had Allergy.
Table 8. Comments: 1. Of 30 cases studied
28 cases (93.3%) had Poor appetite and
2 (6.7%) had good appetite.
2. Large majority of the cases studied had Poor appetite.
Table 9. Comments: 1. Of 30 cases studied,
26 cases (86.7%) had Mixed type of diet
4 (13.3%) had Vegetarian type of diet.
2. Large majority of the cases studied had Mixed type of diet.
Table 10. Comments: 1. Of 30 cases studied, 28 cases (93.3%) did not have any addiction
2 (6.7%) had Smoking/Alcohol habit
2. Large majority of the cases studied did not have any addiction
Table 11. Comments: 1. Of 30 cases studied, 15 cases (50.0%) had less than 7Hrs of sleep duration and 15 (30.0%) had 7-12Hrs of sleep duration.
Table 12. Comments: 1. Of 30 cases studied, 11 cases (36.6%) had Lower social class
2 (6.7%) had Lower Middle Class
12 cases (40.0%) had Upper Middle Class
and 5 (16.7%) had Upper class.
2. Majority of the cases studied had Upper middle class.

Table 13-17. Compounds 1-4 isolated from methanolic extract of seeds of Lens culinaris Medik. Click here to view full image

Table 13. Comments: 1. Of 30 cases studied, 9 cases (30.0%) had Thin built, 2 (6.7%) had Muscular and Thin built, 3 (10.0%) had Muscular built, 4 cases (13.3%) Muscular and Broad built, 6(20.0%) had fatty built and 6 (20.0%) had Fatty and Broad built.
2. Majority of the cases studied had Thin Built.
Table 14. Comments: 1. Of 30 cases studied, 4 cases (13.3%) had pale pallor and 26 cases (86.7%) did not have pallor.
2. Majority of the cases studied did not have pallor.
Table 15. Comments: 1. Of 30 cases studied, 19 cases (63.3%) had Day time itching
11 cases (36.7%) had night time itching.
2. Majority of the cases studied had day time itching.
Table 16. Comments: 1. Of 30 cases studied, 25 cases (83.3%) did not have any family history and 5 cases (16.7%) had family history (first degree).
2. Majority of the cases studied had no family history.
Table 17. P-values by repeated measures analysis of variance (ANOVA).
P-value <0.05 is considered to be statistically significant. *P-value <0.05, **P-value <0.01, ***P-value <0.001. Comments: 1. The average UAS score is significantly higher at visit 1 compared to visit 2 UAS score (P-value<0.05). The mean % reduction in UAS score at visit 2 was 3.56% compared to the UAS score at visit 1. 2. The average UAS score is significantly higher at visit 1 compared to visit 3 UAS score (P-value<0.001). The mean % reduction in UAS score at visit 3 was 25.61% compared to the UAS score at visit 1. The average UAS score is significantly higher at visit 1 compared to visit 4 UAS score (P-value<0.001). The mean % reduction in UAS score at visit 4 was 35.96% compared to the UAS score at visit 1.

DISCUSSION

An open label clinical study conducted on 30 patients. Baseline history was obtained to determine the inclusion criteria of the patients. The baseline assessment included personal data, a description of symptoms, & details of past medical history. After obtaining the baseline data, all the patients underwent a complete clinical examination. The patients were investigated for B.S.L-R in first visit. All the patients received same dosage of Unani drug for decided period. 37 patients were enrolled in the study (26 Males and 11 Females). 30 patients (19 males & 11 females) completed the study with excellent drug compliance. & 7 patients were lost to follow-up. Results of the study showed that among the 30 patients with Shara (Urticaria) most of the patients (12) were between the age group (less than 30 years). 11 cases had age 30-39 years & 7 cases were of >=40 years. This prevalence of disease according to age coincides with the description of Harrisons Principles of Internal Medicine, in which he described that “Persons in any age group may experience acute or chronic urticaria and/or angioedema, these lesions increase in frequency after adolescence, with the highest incidence occurring in persons in the third decade of life”4
While studying the gender wise distribution of patients, it was observed that 19 patients were male and 11 patients were female. Cecil Textbook of Medicine mentioned about prevalence as “Urticaria /angioedema occur in 15 to 25% of individuals at some times during their life and can affect both genders and all races. Acute urticaria is more common in young adults and children. Chronic urticaria is more common in adults, affecting women (75% of cases) more often than men”6 .My study is not supporting this data. This may be because females shy to & not willing to have their check up with male doctor. Many of them prefer female doctors. There is no exact statistical data available about the incidence of disease with reference to religion. In our study it was found that most of the patients were Muslims (27).Probably due to the situation of our Hospital in Muslim dominated area. When we study the distribution of patients according to their Occupation it was found that most of the patients were students (10) & service sector (8), followed by self employed& Housewives (6 each). One of the reasons for Students being patients would be, the hospital is situated in student’s campus. In other observation it was noticed that (26) patients were having mixed dietary habits. 4 patients were having vegetarian diet. It is mentioned that the food additives tartrazine( E 102) ,Sunset yellow ( E 10), Benzonate Preservative ( E210-219 ), Butylatedhydroxytoulene ( E321 ) are responsible for Urticaria. These additives are found in non-vegetarian diet9 High incidence of Shara (Urticaria) was found in upper middle class (12) followed by lower class (11) of our society. Upper class (5) & lower middle class (2) patients were from this sector.
Mizaj is an important factor in Unani system of medicine. Mizaj of the patients was calculated in cases as per the standard parameter described as “Ajnas-e-Ashra” in classical Unani literature. It was found that most of the patients (13) out of 30 were having Safravi Mizaj.(12) were having Balghami Mizaj.(5) patients of Damvi Mizaj were found. This description gives strength to the observation of classical Unani literature in which “Safra” & “Balgham” were described as most important cause for the Shara. Patient of Shara, with Saudawi Mizaj, not found in our study.
In present study we have observed that out of 30 patients (5) patients were having family history of the disease. There is no adverse effect noted in present study. The patients were assessed clinically through Urticaria Assessment Score (UAS)43, 44. It is internationally used method to measure the efficacy of test drug in clinical study for Urticaria
The following observation was made after the completion of the study: (1) The average UAS score is significantly higher at visit 1 compared to visit 2 UAS score (P-value<0.05). The mean % reduction in UAS score at visit 2 was 3.56% compared to the UAS score at visit 1. (2) The average UAS score is significantly higher at visit 1 compared to visit 3 UAS score (P-value<0.001). The mean % reduction in UAS score at visit 3 was 25.61% compared to the UAS score at visit 1. (3) The average UAS score is significantly higher at visit 1 compared to visit 4 UAS score (P-value<0.001). The mean % reduction in UAS score at visit 4 was 35.96% compared to the UAS score at visit 1. The basic line of treatment (Usool-e-Ilaj) in shara is:  Mussaffiyat-e-Khoonadvia (Bloood purifying drugs)  Mussakin-e-Hiddat (Soothing of heat)  Munzijwa mushil-e-balgham  Mushil-e-Safra  MedawaamakaTanqiya (Purification of stomach & Intestine)  Mufattit-te-masamaat-e-Jild (Opening of skin pores)  Islah-e-hazam (Improvement of digestion)  Islah-e-ghiza (Improvement of diet)  Avoid things that causes hypersensitivity According to American Journal of Pharm-Tech Research 2012, Ajwain has found a special property of Antihistaminic effect .Hence we can say that our study also supports this observation. Many of Unani Hakims like Hakim GhulamJilani (Makhazan-ul-Ilaj) &AllamaNajibuddinSamarqandi (Sharahasbab) & Hakim Ajmal Khan (Hazique) &Abul-Mansoor-ul-HasanQamari” (Ghina mina) mentioned in their books about the causes of Shara (Urticaria) as “Fasaad-e-Hazam”, “Balghamshor” “& “Menstrual disorders” & “der-e-hazamGhizakaistemaal” & as a result “loss of appetite” may happen. Hakim Sir Godhawi (MakhazanulMufradat-Ma-Murrakabat-KhwasulAdvia) & Hakim UsmaniMd Imran (TanqivulMufradat) mentions about Ajwain functions in great details. Like Ajwain removes Phlegm fasad, Digestive (Hazim), Appetizer(Mushtahi), Diuretics, Emmeneagogue(Mudir-e-haiz), Antiseptic(daf-e-Ta’ffun), Detergent(Jali), Calorific(Musakhkhin), Anti-inflammatory.

CONCLUSION

Keeping in mind all these important facts we think “teacher of Avicenna” Great hakim “Abul-Mansoor-ul-HasanQamari” in his book “Ghina mina” mentioned the use of “Safoof-e-Ajwain” in “Urticaria” which ultimately “looks after” many of the cause of Shara (Urtcaria) & helps the patient to improve from Urticaria. Many of these functions of ajwain had been confirmed & supported by data from modern aspects.
Hence we can say that the drug formulation has action on symptoms of Shara (Urticaria)
LIMITATIONS & FUTURE DIRECTION
The research involves the patients attending the hospital’s outpatient department. Therefore results of this study cannot be representative of national data. The sample size, randomization, comparison, safety parameters, duration of treatment, micro level specification of type of urticaria, control group which could have possibly influenced the research was largely ignored. Future studies need to address the above issues & issues related to management of urticaria in special population like children, pregnant women, lactating mothers, patients of urticaria with renal & hepatic disorders & Immuno-compromised patients and those patients with the age above 60 years .

CONFLICT OF INTEREST
None declared.

ACKNOWLEDGEMENT
I acknowledge to Dr. Abdul Hamid, Dr. Ismail, Mother, for their support.

REFERENCES
Clive EH, Ruth A, Malcom W. Chronic urticaria. Journal of the American Academy of Dermatology. 2002; 46:645–57.
Czarnetzki BM. The history of urticaria. International Journal of Dermatology. 1989;28:52-57.
Goldman, Ausiello, Arend, Armitage, Clemmons, Drazen, et al., editors. Cesil Medicine. 23rd ed. Philadelphia: Saunders Elsevier; Ch. 273, 466, 2007.
Hakim A, Tabri. Al-Moalijat e Buqratiya, New Delhi: CCRUM & AYUSH. 1997. p.206-210, 144-147.
Harrison TR, Petersdorf RG, Resnick WR, Wilson JD, Wintrobe MM, Martin JB,Dan LL, et al., (eds.). Harrison’s Principles of Internal Medicine. 18th ed. New York. McGraw Hill. 2012. p. 2711-2713, 4321.
Ibn-e-Sina AA, Al Qanoon Fit Tib (Urdu translation by Kantoori GH), Vol.4, New Delhi: Idara Kitabush Shifa. p.1262.
Jurjani I, Zakheera Khwarizam Shahi (Urdu translation by Khan HH), Vol.7, New Delhi: Idara Kit bush Shifa; 2010. p. 16-19.
Khopkar U (ed). Urticaria and Angioedema. In: An Illustrated handbook of skin diseases & sexually transmitted Infections; 6th Edition. Mumbai. Bhalani Publishers; 2009; p. 99-101.
Klaus W, Lowella A, Goldsmith S, Stephen IK, Barbara AG, Amy S et al., editors, Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York: McGraw Hill, 2008. p. 330.
Majoosi AA. Kamil-us-Sana’a (Translated by Hkm. Gulam Hussainkantoori); New Delhi: Published by CCRUM, Dept. of AYUSH, Ministry of Health & Family Welfare, Govt. of India; 2010. p.108-110,233-235,435-436.
Marshall SE, Immunological Factors in Disease. In S Nicki RC, Brian RW, Stuart HR (eds.). Davidson’s Principles & Practice of Medicine.International edition. ISBN-13: 978-0-7020-3084-0 .21st ed. Edinburgh. Churchil Livingstone Elsevier. 2010. p. 86.
Maurer M, Weller K, Bindslev JC, Gimenez-AA, Bousquet PJ, Bousquet J, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report. Allergy. 2011; 66 p. 317–330.
Richard W, John H, John S, Mark D. Clinical Dermatology: 4th ed. Massachusetts: Wiley Blackwell Publishers, 2008. p. 104-109, 4.
Rook AJ. The historical background. In: Warin RP, Champion RH (eds.) Urticaria. London: Saunders, 1974. p. 1–2.
Tony Burns, Stephen Breathnach, Neil Cox, Christopher Griffith’s, Rook’s Textbook of Dermatology, Vol. 1,8th ed. p. 3.1-3.53,4.1-4.11,22.1 22.30
Vibhu M (section ed. Dermatology), Jaiswal AK, Nagesh TS., Abnormal Vascular Responses. In Munjal YP Sharma SK, Agarwal AK, Gupta P, Kamath SA, Nadkar MY (eds) ; API Textbook of Medicine: Vol I,9th ed. Mumbai; API Publishers, 2012. p. 491-493,462.
Zuberbier T, Asero R, Bindslev-JC, Walter CG, Church M, Gimenez-AA, et al. EAACI/ GA (2) LEN/EDF/WAO guideline: Management of Urticaria. Allergy. 2009;64; 1427–1443.