Therapeutic consideration and treatment of conjunctivitis, food and skin allergies

By Yashika Kapoor on February 26, 2018

The allergic disorders present a wide array of manifestations in the humans, demanding unique therapeutic strategies. The previous article shed light on treatment strategies for lethal Anaphylaxis, Allergic Rhinitis & Asthma. The ocular and skin allergies not only compromise the quality of life but also makes the patient self-conscious about appearance. The food allergies, on the other hand, compromise the ability to intake food, associated with hassles of finding alternative supplements. These allergies could also trigger severe allergic reactions such as lethal anaphylaxis. Hence, the present article discusses the therapeutic options available for respective allergic diseases.

Allergic conjunctivitis an ocular allergy

Allergic conjunctivitis is an ocular allergy involving an inflammatory process which is bilateral and self-limiting in nature. It is divisible into seasonal allergic conjunctivitis and perennial allergic conjunctivitis. Furthermore, it also finds a strong association with allergic rhinitis as 90% of the patients suffer at least one episode of allergic conjunctivitis (Berger 2005). The inflammatory reaction results from either IgE mediated immune response or immediate hypersensitivity reaction. Besides these, the allergic reaction can also result from neurogenic mechanisms, adhesion molecules and systemic immune cff. Both seasonal allergic conjunctivitis and perennial allergic conjunctivitis are mast cell-g, type-1 hypersensitive, acute allergic reactions (Sánchez et al., 2011).

The binding of IgE with FcεRI receptors on mast cells causes changes in the cell membrane permeability. This results in the release of inflammatory mediators such as histamine, leukotriene, Carboxypeptidase A, serotonin, prostaglandin, Cathepsin G, Eosinophil, Neutrophil and Platelet-activating factor. It causes a biphasic response: early and late phase. The early phase response involves itching, swelling, redness, tearing, and oedema. Whereas, the late phase involves infiltration of basophils, neutrophils, and eosinophils.

Therapeutic considerations for allergic conjunctivitis

A large number of drugs are available to counter the effect of mediator molecules and bring relief from the allergic reaction. Besides these treatments, allergic conjunctivitis can also benefit from allergen-specific immunotherapy, same as allergic asthma. Immunotherapy is known to improve seasonal allergic conjunctivitis symptoms and medication usage.

A wide range of drugs for allergic conjunctivitis

The available treatment options for allergic conjunctivitis as mentioned by Carr et al. (2016) are as follows:

Topical histamines

Mode of action
Therapeutic impact
Adverse effects
Inhibition of histamine receptors on nerve endings and blood vessels on the surface of the mucosa. Reduction in itchiness and conjunctival hyperemia. Limited duration of effect; Burning, Dryness.

Table 1: Drug action for Topical Histamines
Examples: Levocabastine, Emedastine difumarate

Antihistamine-vasoconstrictor combinations

Mode of action
Therapeutic impact
Adverse effects
Stimulation of alpha adrenergic receptors. Reduction of ocular and conjunctival hyperemia. Not recommended for a long time due to a reduction in efficacy.

Table 2: Drug action for antihistamine-vasoconstrictors

Examples: Naphazoline-pheniramine, Naphazoline-antazoline

Leukotriene receptor antagonists

Mode of action
Therapeutic impact
Adverse effects
Prevention of leukotriene binding to conjunctival receptors. Reduction in inflammation signal. Slower onset of action; Not preferred for monotherapy.

Table 3: Drug action for leukotrienes

Examples: Montelukast

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Mode of action
Therapeutic impact
Adverse effects
Inhibition of inflammatory mediator production by acting on cyclooxygenase enzymes                         Disruption of the inflammatory cascade. Reduction in pain, inflammation and itching. Limited efficacy; No effect on chemosis or swelling.

Table 4: Drug action for NSAIDs

Examples: Ketorolac, Nepafenac, Bromfenac

Corticosteroids

Mode of action
Therapeutic impact
Adverse effects
Inhibition of production of late phase response mediators.

Interruption of the inflammatory cascade.

Potent anti-inflammatory action. Increase in intraocular pressure, a risk of cataract due to long-term use.

Table 5: Drug action for corticosteroids

Examples: Prednisolone, Loteprednol, Difluprednate

Mast cell stabilizers

Mode of action
Therapeutic impact
Adverse effects
Inhibition of release of histamine from mast cells.

Prevention of mast cell degranulation and interruption of the inflammatory cascade.

Stabilization of mast cell and inhibition of late response. Long-term usage causes intolerance.

Table 6: Drug action for Mast cell stabilizers

Examples: Lodoxamide tromethamine, Pemirolast potassium, Nedocromil sodium, Cromolyn sodium

Dual acting agents

Mode of action
Therapeutic impact
Adverse effects
First line therapeutics.

Posses both antihistamine and mast cell stabilizing functions thus more effective than single medication.

Alleviates multiple symptoms and blocks the feed-forward cycle.

Table 7: Drug action for dual acting agents

Examples: Ketotifen, epinastine, Olopatadine

Allergies due to food

Food allergies are hypersensitive reactions, occurring due to specific food substance-related stimuli and resulting from immune mechanisms. In the case of non-immune hypersensitive responses, the phenomenon is termed as non-allergic food hypersensitivity or food intolerance (Olivier, 2013). Below shown is the classification of food allergies as per the immune response.

Type of allergy
Features
Diseases included
Atopy Personal or familial predisposition to IgE production                                                 Increase in total serum IgE levels  Frequently seen in children Dermatitis, Asthma, Allergic rhinitis
Monoallergy IgE mediated hypersensitive reaction in absence of IgE increase in serum in non-atopic individuals                                                   No pre-disposing factors Anaphylaxis
IgE mediated allergy Non-atopic, Non-IgE associated allergy         Normal IgE serum levels, non-reactive skin tests Intrinsic asthma, dermatitis, rhinitis

Table 8: Types of food allergies with respect to immune response (Olivier, 2013)

These allergies develop in two stages, namely, sensitization and elicitation. Sensitization involves the establishment of pathways of reaction to the allergen. On the other hand, elicitation involves the inflammatory immune response during re-exposure to the allergen. The allergic response perpetuation results from the cytokines and chemokines produced by mast cells and basophils (Syed, Kohli, & Nadeau, 2013).

Therapeutic considerations for food allergies

The treatment of food allergy involves the removal of sensitizing agent or the allergen from the system. These allergies can develop from reactions to more than one food,  thus correct diagnosis to detect unsuspecting agents is important. However, there is no particular or standard cure for food allergies. Precautionary measures on the part of patients and dietary elimination of allergens is advised (Olivier, 2013).

Immunotherapy and desensitization mechanisms form the basis of treatment. Immunotherapies can be either food specific or non-food specific. Non-specific therapies do not target a specific allergen and are advantageous in desensitizing the individual to a number of different allergens. Examples include herbal formulations, anti- IgE therapies, use of probiotics, and parasites. Food-specific therapies involve Sublingual immunotherapy, gene therapy, and delivery of bacterial adjuvants with allergens which skew the immune system(Syed, Kohli, & Nadeau, 2013).

Allergic reactions involving Skin

A range of allergic conditions affects skin such as atopic dermatitis, angioedema, contact dermatitis, psoriasis, urticaria and autoimmune blisters. Most of these allergies are chronic, proliferative, and inflammatory in nature, influenced by both genetic and environmental factors. Here we discuss atopic dermatitis and urticaria.

Atopic dermatitis

The skin becomes dry and itchy, and eczematous skin lesions relapse. It is one the common occupational disease, exhibiting heterogeneous pathophysiology. Below shown is the mechanism of atopic dermatitis, which involves the interaction of impaired innate immunity and distorted adaptive immunity. Cytokines are the mediator molecules, resulting in dysfunction of the role of skin as a barrier. Also, filaggrin gene mutations play an important role in atopic dermatitis (Fonacier, Dreskin, & Leung, 2010).

Therapeutic considerations for atopic dermatitis

Atopic dermatitis treatment can follow a combination of emollient, anti-inflammatory, and antimicrobial therapy. The traditional treatments include the application of topical anti-inflammatory agents such as corticosteroids or calcineurin inhibitors. Proactive therapy is yet another approach. It involves the long-term, low-dose anti-inflammatory therapy besides emollient treatment of unaffected skin. Some of the emerging strategies involve subcutaneous immunotherapy and target therapy. Acupuncture treatment has also shown appreciable efficacy (Wollenberg & Feichtner, 2013).

Urticaria

Urticaria is the appearance of pruritic, edematous erythematous lesions of different sizes. These lesions exhibit blanching under pressure. Angioedema, on the other hand, is a form of urticaria exhibiting deeper swelling of the skin. An individual may show either of them or both together. Below shown is the list of causes resulting in Urticaria.

Aetiology

Mode of action

Idiopathic Not known
Immunological
Autoimmune Binding of IgG autoantibodies to IgE receptors on mast cells.
IgE Cross-linkage of SIgE on mast cells due to contact with an allergen.
Immune complex Due to infections such as hepatitis, dental infections, urinary tract infections, or sinusitis.
Non-Immunological
Physical Histamine release triggered due to physical factors such as sweating, pressure, vibration, water, sunlight, cold, or heat.
Drug treatment Sensitivity to cyclooxygenase inhibitors.

Direct release of histamine from mast cells due to opiates.

Dietary pseudo allergens Due to natural salicylates, preservatives such as sulfites, nitrates or nitrites, or food colours containing azo dyes.

Egg whites, strawberries, and shellfish also trigger histamine release.

Medical conditions Due to diseases such as lupus erythematosus, Sjögren’s syndrome, autoimmune thyroid disease, hypothyroidism and hyperthyroidism.

Table 9: Different aetiologies for urticaria (Deacock, 2008)

Therapeutic considerations for urticaria

Urticaria may not always be an outcome of an allergic reaction. The treatment options include administration of second-generation H1 antihistamines such as cetirizine, desloratadine, fexofenadine, leukotriene receptor antagonists such as montelukast or corticosteroids. Corticosteroid treatment is preferred for patients showing refractory urticaria. The topical treatments such as doxepin cream having anti-H1 and H2 activity also provides symptomatic relief (Bernstein et al., 2014). Moreover, the step treatment approach is also preferred for Urticaria as shown below:

Step treatment for Urticaria
Image 1: Step treatment for Urticaria (Bernstein et al., 2014)

Availability of treatment options

The discussion on conjunctivitis and skin allergies show that considerable treatment options are available for both of them. In contrast to this, the broad horizon of causative agents of food allergies makes the design of a standard treatment difficult. However, the treatment of immune reactions resulting from intake of allergic foods uses the standard treatment pertaining to the respective condition.

References

  • Bernstein, J. A., Lang, D. M., Khan, D. A., Craig, T., Dreyfus, D., Hsieh, F., … Blessing-Moore, J. (2014). The diagnosis and management of acute and chronic urticaria: 2014 update. Journal of Allergy and Clinical Immunology, 133(5), 1270–1277.
  • Carr, W., Schaeffer, J., & Donnenfeld, E. (2016). Treating allergic conjunctivitis: A once-daily medication that provides 24-hour symptom relief. Allergy & Rhinology, 7(2), e107.
  • Deacock, S. J. (2008). An approach to the patient with urticaria. Clinical & Experimental Immunology, 153(2), 151–161.
  • Fonacier, L. S., Dreskin, S. C., & Leung, D. Y. M. (2010). Allergic skin diseases. J Allergy Clin Immunol, 125(2), 138–149.
  • Mishra, G. P., Tamboli, V., Jwala, J., & Mitra, A. K. (2011). Recent patents and emerging therapeutics in the treatment of allergic conjunctivitis. Recent Patents on Inflammation & Allergy Drug Discovery, 5(1), 26–36.
  • Olivier, C. E. (2013). Food Allergy. Journal of Allergy & Therapy, 3(4), 1–7.
  • Sánchez, M. C., Fernández Parra, B., Matheu, V., Navarro, A., Ibáñez, M. D., Dávila, I., … Valero, A. (2011). Allergic conjunctivitis. J Investig Allergol Clin Immunol, 21(2), 1–19.
  • Syed, A., Kohli, A., & Nadeau, K. C. (2013). Food allergy diagnosis and therapy: where are we now? Immunotherapy, 5(9), 931–944.
  • Wollenberg, A., & Feichtner, K. (2013). Atopic dermatitis and skin allergies – update and outlook. Wollenberg, A. Feichtner, K., 68(12), 1509–1519.

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