A case of bronchial asthma and allergic rhinitis exacerbated ... - MedIND

case report

A case of bronchial asthma and allergic rhinitis exacerbated during Cannabis pollination and subsequently controlled by subcutaneous immunotherapy Raj Kumar, Nitesh Gupta

Access this article online

ABSTRACT

Website: www.ijaai.in

DOI: 10.4103/0972-6691.124399 Quick Response Code:

The prevalence of bronchial asthma and allergic rhinitis has been on the rise in India. Cannabis is reported to be one of the allergenically important airborne pollen identified by the clinico‑immunologic evaluation in the spring season in India. We report a case of 38‑year‑old male patient with typical clinical manifestations of bronchial asthma and allergic rhinitis that classically exacerbates during the pollination period of Cannabis. On evaluation, the patient was found to be significantly sensitized to Cannabis sativa. Subsequent subcutaneous immunotherapy leads to marked improvement in control of asthma as well as improved quality‑of‑life. Key words: Allergic rhinitis, bronchial asthma, Cannabis sativa, subcutaneous immunotherapy

INTRODUCTION The prevalence of allergic diseases such as bronchial asthma and allergic rhinitis has been on the rise all over the world including developing countries like India. The number of people suffering from allergy is 20% to 30% of population and pollinosis alone accounts in about 10‑15% of the world inhabitants.[1‑3] Hemp (Cannabis sativa), a plant of Asian origin belongs to Cannabaceae family. It is usually cultivated but may grow wild in some places. C. sativa is, an anemophilous plant bears very light pollen which can be transported over long distances and its allergenic capability varying from being mild to high.[4] In an analysis of the qualitative and quantitative prevalence of pollen allergens from India, Cannabis was reported to be one of the allergenically important airborne

pollen identified by the clinico‑immunologic evaluation in the spring season (February‑April).[5] In a recent retrospective analysis of skin prick testing (SPT) in 918 patients suffering from bronchial asthma and/or allergic rhinitis, Cannabis was found to be offending allergen in 2.18% cases. [6] Stokes et al. [7] evaluated the patients complaining of asthma and/or rhinitis symptoms on exposure to Cannabis plants during the summer and concluded Cannabis skin test positive patients demonstrates typical symptoms of allergic respiratory disorders during pollination periods. A review of the literature revealed though the allergic potential of Cannabis being documented for more than 60 years, yet the studies indicating clinical significance of its pollen as an aeroallergen and its management has been sparse.

Department of Respiratory Allergy and Applied Immunology, National Centre of Respiratory Allergy, Asthma and Immunology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India Address for correspondence: Dr. Raj Kumar, Department of Respiratory Allergy and Applied Immunology, National Centre of Respiratory Allergy, Asthma and Immunology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi ‑ 110 007, India. E‑mail: [email protected]

Indian Journal of Allergy, Asthma and Immunology | Jul-Dec 2013 • Volume 27 • Issue 2

143

Kumar and Gupta: Cannabis sensitization and immunotherapy

CASE REPORT The present case report is about a 38‑year‑old human immunodeficiency virus negative male doctor, current smoker who presented to our Institute for evaluation of episodic breathlessness accompanied with wheeze which he had been suffering for a period of 18 years. These episodes were associated with sneezing, rhinorrhea and nasal itching. The symptoms had characteristic worsening during the spring season (February‑April). General physical examination revealed no pallor, clubbing or cyanosis. He was tachypneic with a respiratory rate of 26/min. On auscultation, vesicular breath sounds of equal intensity were audible bilaterally along with rhonchi. On serological investigation, hemoglobin 12.07 g/dl, white blood cell count 8900/µl, eosinophil 7%. The radiology was within the normal limits. At presentation, patient has been on inhaled corticosteroid and long acting beta‑2 agonist combination therapy for last 8 years and was compliant, but requires additional oral corticosteroid therapy frequently for control of his symptoms. Patient also has to take frequent doses of oral anti‑histamines to control the nasal symptoms. The history of the patient was suggestive of uncontrolled bronchial asthma with allergic rhinitis, with worsening during the spring season. The family history was negative for atopy. On evaluation, patient was found to have symptom aggravation during the spring season while having his morning walk through the open spaces near his home. On the other hand, the symptoms are of lesser intensity on avoidance of that zone. On geographical survey, rich flora of C. sativa was observed in the surrounding locale. Patient also denied any history of smoking marijuana. Patient underwent SPT, the reaction was significantly positive (4+) with pseudopodia formation against C. sativa [Figure 1]. Subsequently subcutaneous perennial immunotherapy (IT)

versus C. sativa was initiated with 1:5000 w/v diluted antigen and the injections were given 2 times a week starting from 0.1 ml and increased in every injection by 0.1 ml. The further schedule is labeled in Table 1.[8] After a maintenance dose of 1 year, patient had a well‑controlled asthma and rhinitis and is currently following up on a maintenance dose. The patient reports of having resumed his march through the same area devoid of episodes of exacerbations.

DISCUSSION The earliest evidence of potential allergenicity of Cannabis pollen comes from a case report of a female physician, from Omaha who developed symptoms of rhino‑conjunctivitis while marching near pollinating plants. Subsequently, on SPT with hemp pollen she developed an anaphylactic reaction.[9] Anaphylactic response, in a 29‑year‑old female smoking marijuana cigarette for the first time, was documented in 1971 and further confirmed by SPT and passive transfer studies. It was suggested that tetrahydrocannabinol was accountable for immunological response. Since then, isolated cases of allergic hypersensitivity to C. sativa have been described, urticaria and contact dermatitis due to handling of Cannabis plants[10,11] and anaphylaxis due to Cannabis ingestion.[12] Paradoxically, the protective action of Cannabis against allergies has also been described.[13] The study by Stokes et al.[7] hypothesized that Cannabis might be clinically important allergen especially in patients complaining of asthma and/or rhinitis symptoms. The hemp pollen accounted for 36% of the total pollen count. In a sample of pollen‑allergic patients, 78% were sensitive to C. sativa pollen and 73% presented symptoms during the pollination season. Thus a strong association was observed between skin test reactivity, respiratory symptoms and pollination period. However, since the patients also had concomitant sensitization, the authors proposed further additional studies. Our patient also had a significant skin test reactivity correlating both with worsening of symptoms as well as the pollinating season, thus demonstrating Cannabis allergic sensitization. In a cohort of 17 individuals with symptoms suggestive of marijuana sensitivity, 15 were suffered from rhinitis Table 1: Immunotherapy schedule of the patient

Figure 1: Skin prick testing showing the reaction was significantly positive (4+) with pseudopodia formation against Cannabis sativa 144

Concentration of antigen 1:5000 1:500 1:50 1:50 1:50 1:50 1:50 1:50

Duration and dose Two times a week, from 0.1 ml to 0.9 ml Two times a week, from 0.1 ml to 0.9 ml One time a week, from 0.1 ml to 0.5 ml One time in 2 weeks, 0.6 ml One time in 3 weeks, 0.7 ml One time a month, 0.8 ml One time a month, 0.9 ml One time a month, 1.0 ml – highest maintenance dose


Kumar and Gupta: Cannabis sensitization and immunotherapy

and conjunctivitis on inhalational exposure. [14] Other manifestations were urticaria, periorbital angioedema, wheezing and sinusitis. All individuals reported symptoms on repeated exposures and cessation following avoidance of marijuana. In current case, the patient too had aggravation of symptoms on repeated exposures and reduced intensity on avoidance of allergen. The identification of five C. sativa IgE‑binding proteins, ranging from 10 to 68 kDa and a 9‑kDa lipid transfer protein have been implicated with type 1 sensitization to Cannabis plant. In Cannabis sensitized patients cross‑reactivity has been observed with tomato, tobacco, latex, ragweed, pigweed and Aspergillus.[15‑17] In our case, the SPT was performed against 58 aero‑allergens including Aspergillus but only Cannabis was positive. Allergen specific immunotherapy works through enhancing immune tolerance mechanisms and reduction in the lymphoproliferative responses to allergens. It is the most effective therapeutic approach for dysregulated immune response toward allergens and shifting of immune response from the allergic Th2 to non‑allergic Th1.[18] IT has been highly effective in management of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity.[19,20] In a study by Gaur et al.[21] half of patients suffering from seasonal allergic rhinitis exhibited substantial reduction in their symptom score as well as drug intake after 2 years of IT with mixed allergen vaccines. A study comparing inhaled budesonide with IT in subjects of perennial asthma; IT resulted in slow but steady improvement which was long lasting and did not decline rapidly in comparison to budesonide therapy. [22] In another prospective study of subjects suffering from asthma and rhinitis IT showed significant improvement in the symptom score, forced expiratory volume in first second, and immunological parameters. [23,24] Similar to results above, our case also showed slow, steady and sustained response to IT with marked improvement in his symptoms, quality‑of‑life and significant reduction of his drugs dosages. To the best of our knowledge, this is the unique study in which IT against Cannabis has been initiated and the response being documented. The above case attempts to highlights the importance of familiarity with local aero‑allergen prevalence and difficulty in assessing Cannabis exposure history and thus increased awareness of Cannabis as a potential aeroallergen should be nurtured. The identification of the allergen and subsequent initiation of IT with dramatic response to symptoms and quality‑of‑life in the current case may denote a role of IT in management of Cannabis allergy.

REFERENCES 1. Pekkanen J, Remes ST, Husman T, Lindberg M, Kajosaari M, Koivikko A, et al. Prevalence of asthma symptoms in video and written questionnaires among children in four regions of Finland. Eur Respir J 1997;10:1787‑94. 2. Woolcock AJ, Bastiampillai SA, Marks GB, Keena VA. The burden of asthma in Australia. Med J Aust 2001;175:141‑5. 3. Anthracopoulos M, Karatza A, Liolios E, Triga M, Triantou K, Priftis K. Prevalence of asthma among schoolchildren in Patras, Greece: Three surveys over 20 years. Thorax 2001;56:569‑71. 4. Mayoral M, Calderón H, Cano R, Lombardero M. Allergic rhinoconjunctivitis caused by Cannabis sativa pollen. J Investig Allergol Clin Immunol 2008;18:73‑4. 5. Singh AB, Shahi S. Aeroallergens in clinical practice of allergy in India‑ ARIA Asia Pacific Workshop report. Asian Pac J Allergy Immunol 2008;26:245‑56. 6. Kumar R, Sharan N, Kumar M, Bisht I, Gaur SN. Pattern of skin sensitivity to various aeroallergens in patients of bronchial asthma and/or allergic rhinitis in India. Indian J Allergy Asthma Immunol 2012;26:66‑72. 7. Stokes JR, Hartel R, Ford LB, Casale TB. Cannabis (hemp) positive skin tests and respiratory symptoms. Ann Allergy Asthma Immunol 2000;85:238‑40. 8. Gaur SN, Singh BP, Singh AB, Vijayan VK, Agarwal MK. Guidelines for practice of allergen immunotherapy in India. Indian J Allergy Asthma Appl Immunol 2009;23:1‑20. 9. Maloney ES, Brodkey MH. Hemp pollen sensitivity in Omaha. Nebr Med J 1940;25:190‑1. 10. Williams C, Thompstone J, Wilkinson M. Work‑related contact urticaria to Cannabis sativa. Contact Dermatitis 2008;58:62‑3. 11. Majmudar V, Azam NA, Finch T. Contact urticaria to Cannabis sativa. Contact Dermatitis 2006;54:127. 12. Stadtmauer G, Beyer K, Bardina L, Sicherer SH. Anaphylaxis to ingestion of hempseed (Cannabis sativa). J Allergy Clin Immunol 2003;112:216‑7. 13. Clement YN, Williams AF, Aranda D, Chase R, Watson N, Mohammed R, et al. Medicinal herb use among asthmatic patients attending a specialty care facility in Trinidad. BMC Complement Altern Med 2005;5:3. 14. Tessmer A, Berlin N, Sussman G, Leader N, Chung EC, Beezhold D. Hypersensitivity reactions to marijuana. Ann Allergy Asthma Immunol 2012;108:282‑4. 15. de Larramendi CH, Carnés J, García‑Abujeta JL, García‑Endrino A, Muñoz‑Palomino E, Huertas AJ, et al. Sensitization and allergy to Cannabis sativa leaves in a population of tomato (Lycopersicon esculentum)‑sensitized patients. Int Arch Allergy Immunol 2008;146:195‑202. 16. Armentia A, Dueñas‑Laita A, Bartolomé B, Martín‑Gil FJ, San Miguel A, Castrodeza JJ. Clinical significance of cross‑reactivity between tobacco and latex. Allergol Immunopathol (Madr) 2010;38:187‑96. 17. Kagen SL. Aspergillus: An inhalable contaminant of marihuana. N Engl J Med 1981;304:483‑4. 18. Akdis M, Akdis CA. Mechanism of allergen‑specific immunotherapy. J Allergy Clin Immunol 2007;119:780‑9. 19. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: A practice parameter third update. J Allergy Clin Immunol 2011;127:S1‑55. 20. Gaur SN, Singh AB, Mehta AK. Successful desensitization with honey bee venom: A case report. Indian J Allergy Asthma Immunol 2007;21:69‑7. 21. Gaur SN, Gupta SN, Gupta S. Clinical response of


145

Kumar and Gupta: Cannabis sensitization and immunotherapy immunotherapy in cases of nasobronchial allergy. Indian J Allergy Asthma Immunol 1996;10:65‑8. 22. Shaikh WA. Immunotherapy vs inhaled budesonide in bronchial asthma: An open, parallel, comparative trial. Clin Exp Allergy 1997;27:1279‑84. 23. Srivastava D, Singh BP, Sudha VT, Arora N, Gaur SN. Immunotherapy with mosquito (Culex quinquefasciatus) extract: A double‑blind, placebo‑controlled study. Ann Allergy Asthma Immunol 2007;99:273‑80.

24. Srivastava D, Singh BP, Arora N, Gaur SN. Clinico‑immunologic study on immunotherapy with mixed and single insect allergens. J Clin Immunol 2009;29:665‑73. How to cite this article: Kumar R, Gupta N. A case of bronchial asthma and allergic rhinitis exacerbated during Cannabis pollination and subsequently controlled by subcutaneous immunotherapy. Indian J Allergy Asthma Immunol 2013;27:143-6. Source of Support: Nil, Conflict of Interest: None declared.

Announcement

iPhone App A free application to browse and search the journal’s content is now available for iPhone/iPad. The application provides “Table of Contents” of the latest issues, which are stored on the device for future offline browsing. Internet connection is required to access the back issues and search facility. The application is Compatible with iPhone, iPod touch, and iPad and Requires iOS 3.1 or later. The application can be downloaded from http://itunes.apple.com/us/app/medknow-journals/ id458064375?ls=1&mt=8. For suggestions and comments do write back to us. 146
