Interstitial cystitis and immunotherapy

This is very interesting case. Indeed, activation of mast cells plays an important role in the pathogenesis of bladder pain syndrome/interstitial cystitis. Histamine, a mast cell-derived mediator, can induce inflammation and hypersensitivity of the bladder.

One study evaluated the response to antihistamines based on the expression of histamine receptors in the bladder of these patients. Bladder tissues were collected from 69 BPS/IC patients and 10 control female patients. The expression of the H3R histamine receptor in these patients was further examined in an independent cohort of 10 female patients with BPS/IC and another 10 age-matched female patients. Immunohistochemistry, Western blotting, and quantitative RT-PCR were performed to quantify the expressions of histamine receptors. Statistical analyses of the correlation of histamine receptor expression with antihistamine therapy outcome and severity of disease symptoms was also performed. The expression of four histamine receptors was significantly elevated in bladder pain syndrome/interstitial cystitis (H1R, P < 0.001; H2R, P = 0.031; H3R, P = 0.008; H4R, P = 0.048).

The patients were divided into antihistamine responders (n = 38) and nonresponders (n = 22). No significant correlation was found in the expression of histamine receptors between responder and nonresponder groups. However, significant correlations between the severity of symptoms and H1R (P = 0.003) and H3R (P = 0.045) were found. (Shan et al. 2019)

The histamine metabolite methylhistamine and the unique mast cell protease tryptase are also increased in the 24-h urine of interstitial cystitis patients. The urine histamine metabolite 1,4-methyl imidazole acetic acid and eosinophil cationic protein have been shown to be increased and correlated with bladder mast cell density in interstitial cystitis (Theoharides et al.)

Based on this information, I recommend you try an antihistamine regimen. The regimens that have been utilized include cimetidine, hydroxyzine, and amtitriptyline. The histamine-2 receptor antagonist cimetidine was reported to decrease the median symptom score in 34 patients studied, but with no apparent histological changes in the bladder mucosa. (Thilagarajah et al. 2001) In two open-label studies hydroxyzine (75 mg four times a day titrated over 1 month for 4 months) reduced symptoms by 55% (n = 140). (Theoharides TC. 1993, 1997

In the case of your patient, I would recommend pre-treatment with an aggressive H1 and H2 antihistamine regimen, and if this doesn't work, try a mast cell stabilizer or omalizumab (Lee et al. 2006) to help with your patient's symptoms. I hope this helps you and your patient.

1. Shan H, Zhang EW, Zhang P, Zhang XD, Zhang N, Du P, Yang Y. Differential expression of histamine receptors in the bladder wall tissues of patients with bladder pain syndrome/interstitial cystitis - significance in the responsiveness to antihistamine treatment and disease symptoms. BMC Urol. 2019 Nov 12;19(1):115. doi: 10.1186/s12894-019-0548-3. PMID: 31718622; PMCID: PMC6852726.

2. Theoharides TC, Whitmore K, Stanford E, Moldwin R, O'Leary MP. Interstitial cystitis: bladder pain and beyond. Expert Opin Pharmacother. 2008 Dec;9(17):2979-94. doi: 10.1517/14656560802519845. PMID: 19006474.

3. Thilagarajah R, Witherow RO, Walker MM. Oral cimetidine gives effective symptom relief in painful bladder disease: a prospective, randomized, double-blind placebo-controlled trial. BJU Int 2001;87:207-12

4. Theoharides TC. Hydroxyzine for interstitial cystitis. J Allergy Clin Immunol 1993;91:686-7

5. Theoharides TC, Sant GR. Hydroxyzine therapy for interstitial cystitis. Urology 1997;49(Suppl):108-10

6. Lee J, Doggweiler-Wiygul R, Kim S, Hill BD, Yoo TJ. Is interstitial cystitis an allergic disorder?: A case of interstitial cystitis treated successfully with anti-IgE. Int J Urol. 2006 May;13(5):631-4. doi: 10.1111/j.1442-2042.2006.01373.x. PMID: 16771742.

Sincerely,
Carla M. Davis, MD, FAAAAI