Page 673 - Clinical Immunology_ Principles and Practice ( PDFDrive )

646 ParT fivE Allergic Diseases

keratitis, which is more common and severe in AKC, can be
Immunological Studies in AKC potentiated by topical steroids. Topical tacrolimus is more potent
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In AKC the predominant cell types infiltrating the conjunctival than topical cyclosporine and well tolerated. Facial and lid
tissues are T cells, eosinophils, and neutrophils (Fig. 47.1). As dermatitis should be actively managed, if necessary in conjunction
observed in VKC, increased numbers of activated CD4 T cells, with a dermatologist, whereas lid margin inflammation (blepha-
HLA-DR expression, and cells of the monocyte/macrophage ritis) should be treated with hot compresses followed by lid
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lineage are found in conjunctival biopsy specimens in AKC, hygiene, topical antibiotic, and/or steroid preparations and
as well as mRNA expression of IL-3, IL-4, and IL-5 in the stroma. systemic low-dose antibiotics (especially tetracyclines), all of
However, in AKC there is a significant increase in the expression of which will lessen the need for antiinflammatory and immunosup-
IL-2 mRNA and in the numbers of IFN-γ–expressing T cells, sug- pressive therapy.
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gesting a Th1-mediated inflammation in this disease. Collagen Systemic therapy can be necessary in severe cases, particularly
deposition and conjunctival tissue remodeling are considerable in when surgical therapy is undertaken, and includes steroids,
VKC and AKC, so the production of proinflammatory cytokines cyclosporine, and sometimes other immunosuppressive agents
by infiltrating cells may be the mechanism whereby tissue-resident such as mycophenolate mofetil. All of these carry risks of serious
cells such as conjunctival fibroblasts become involved. side effects and also affect the general atopic picture, so consulta-
tion with the patient’s physician is advisable.
Experimental Model of AKC A significant number of patients require ocular surgery, either
To investigate the immunopathogenic mechanisms involved as a consequence of the disease or because of associated kera-
during AKC, a new clinically more severe model of EAC has toconus. Surgery for AKC includes both elective procedures and
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been developed. In this model, EAC was induced in C57BL/6 emergency interventions and may consist of corneal gluing, patch
mice by systemic immunization and topical daily challenge grafts, corneal transplants (partial or full thickness), conjunctival
with ovalbumin (OVA). OVA-challenged mice exhibited more reconstruction, amniotic membrane grafts, and limbal trans-
severe clinical symptoms compared with other mouse models plantation. These are generally high-risk procedures and often
described above, with chemosis and hyperemia. Because this require support with systemic immunosuppression.
model demonstrated clinical symptoms similar to AKC, it has In summary, allergic disorders of the eye range in severity
been used to show that mast cell, CD4 T cell, and dendritic and duration. Recent studies have increased our understanding
cell numbers are increased during disease, while IL-9, a growth of the molecular mechanisms involved. VKC and AKC require
factor for mast cells, was also upregulated (Mohd Zaki et al, immunosuppressive therapy, which can have serious side effects.
submitted; Fig. 47.3). Although the therapeutic options for treating mast cell–mediated
forms of allergic conjunctivitis have improved, there is still a
Therapy need to find alternative, safer therapies for the more severe and
Therapy for AKC not only aims to control symptoms but also chronic forms.
attempts to modify and reduce serious sight-threatening sequelae;
therefore it should be aggressive. The topical treatment of the Please check your eBook at https://expertconsult.inkling.com/
ocular surface is similar to VKC in that some general therapy for self-assessment questions. See inside cover for registration
may help, antihistamines are not useful, mast cell inhibitors are details.
continued long-term, and steroid and cyclosporine drops are
often required. However, the disease is generally less episodic REFERENCES
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