Gastroenterology case report of mesalazine-induced cardiopulmonary hypersensitivity

Table 1 Summary of previously published cases of mesalazine-induced pulmonary hypersensitivity in patients with inflammatory bowel disease

Ref.	Age (yr)/sex	Disease	Daily dose	Duration of therapy1	Symptoms	EOS	RP	HF	CD4/CD8	BAL	DLCO	Steroid therapy	Rechallenge /recurrence
Le Gros et al[21]	54/F	UC	750 mg	5 d	T, R	ND	I	ND	Ratio: 0.95	Mo: 63% L: 35% E: 1.5%	53%	No	No
Welte et al[22]	67/M	UC	1 g IR	10 d	D, DC, R	ND	I	ND	ND	ND	ND	Yes	No
Reinoso et al[3]	64/F	UC	3.6 g	2 yr	T, D, DC	ND	I	ND	ND	ND	↓	No	No
Lagler et al[23]	66/M	UC	1.5 g	3.5 mo	D, DC	No	I	LP	ND	Mo: 30% L: 67%	54%	Yes	No
Honeybourne et al[24]	30/F	UC	1.6 g	7 mo	T, D, DC, CP	Yes 16%	ND	EP	ND	ND	ND	No	No
Declerck et al[25]	45/F	UC	3 g	3 mo	D	No	I	ND	ND	Mo: 45% L: 38% E: 11%	ND	No	No
Muzzi et al[10]	60/F	CD	2.4 g	ND	T, D, DC	No	I	ND	CD4: 56% CD8: 31% Ratio: 1.80	Mo: 40% L: 55% E: 3%	ND	No	Yes/No
Bitton et al[26]	32/F	UC	4 g	9 mo	T, D, DC	Yes 8.9%	ND	LP/IF	ND	ND	ND	Yes	No
Sviri et al[27]	49/M	CD	3 g	3.5 mo	T, D, DC	No	I	LP/IF	ND	L: 60% E: 10%	80%	Yes	Yes/Yes
Lázaro et al[28]	60/M	UC	ND	4 wk	T, D, DC	Yes	I	IP	ND	Mo: 80% L: 8% E: 10%	67%	No	No
Pascual-Lledó et al[29]	64/F	CD	3 g	2 mo	D, DC, CP	No	I	NL	ND	ND	ND	No2	No
Sesin et al[30]	72/F	UC	1.6-2.4 g3	2 mo	T, D, CP, PC	No	ND4	ND	ND	ND	ND	No	No
Tanigawa et al[31]	35/F	UC	1.5 mg	40 d	T, DC	Yes	I	EP	CD4: 44% CD8: 34% Ratio: 1.3	Mo: 44% L: 49% E: 7%	ND	No	No
Guslandi et al[32]	29/F	UC	3 g	2 d	D, CP	No	ND	ND	ND	ND	ND	No	Yes/Yes
Facchini et al[33]	15/M	UC	2.8 g	4 mo	D, DC	No	A	ND	ND	ND	ND	Yes	No
Zamir et al[34]	23/F	UC	ND	6 wk	F, DC	Yes	ND	ND	ND	ND	ND	Yes	No
Saltzman et al[35]	53/F	UC	ND	4 mo	T, DC, R	Yes 27%	A	EP	ND	E: 79%	ND	Yes	No
Haralambou et al[36]	18/F	UC	1.6 g P.O. + 4 g (enema)	2 mo	T, D, DC, CP	Yes 88%	I	BO	ND	ND	ND	Yes	No
Sossai et al[6]	70/F	UC	2.4 g	3 mo	D, DC	No	I	IP	Ratio: 0.39	Mo: 40% L: 60%	ND	No	N/A5
Pérez et al[37]	50/M	UC	4 g	2 mo	T, D, DC	ND	ND	EP	ND	ND	ND	Yes	No
Foster et al[5]	44/M	CD	2.4-4.8 g	15 mo	T, D, DC	No	A	IP/IF	ND	N: 73%	ND	Yes	No
	30/F	UC	4.8 g	2 yr	T, D, DC, CP	No	A	IP/IF	ND	N: 43%	ND	No	No
	29/F	UC	3.6 g	8 mo	T, D, DC	No	A	IP	ND	ND	19%	Yes	No
Hakoda et al[38]	30/M	UC	2.25 g	4 wk	T, DC	Yes	ND	EP	ND	ND	ND	Yes	No
Actis et al[39]	57/M	UC	ND	2 yr	T, D, DC, CP	No	A	ND	ND	ND	↓	Yes	No
Kohli et al[40]	10/F	UC	3.2 g	2 wk	T, D, DC	Yes 12%	I	IP	ND	ND	ND	Yes	Yes/Yes
Katsenos et al[41]	18/M	UC	ND	1 yr	T, PC	Yes	I	ND	ND	Mo: 15% L: 20% E: 60%	ND	Yes	No
Price et al[11]	28/F	UC	1.2 g	4-5 yr	T, PC	Yes	B	ND	ND	N: 95%	ND	Yes	Yes/No6
Iannone et al[42]	32/F	UC	ND	4 mo	T, DC	No	I	ND	ND	ND	74%	Yes	No
Cilloniz et al[43]	14/M	CD	3 g	8 mo	CP	No	I	IP	ND	Mo: 68% L: 27%	93%	Yes	No
Park et al[44]	35/M	CD	4 g	3 mo	T, DC	Yes 32%	I	EP	CD4: 54% CD8: 41% Ratio: 1.3	L: 31% E: 41%	ND	No	No
Shimizu et al[45]	50/F	UC	ND	4 wk	T, DC	ND	ND	ND	ND	L: 58% E: 20%	ND	No	No
Sposato et al[46]	42/M	UC	3.2 g	8 d	T, CP	Yes 14%	I	ND	ND	Mo: 13% E: 47% N: 34%	ND	Yes7	No
Lamsiah et al[47]	57/F	UC	ND (enemas)	3 mo	T, D, DC	Yes	I	ND	ND	ND	ND	Yes	Yes/Yes8
Kevans et al[48]	17/M	UC	4 g	3 mo	D, DC, CP	Yes 23%	A	ND	ND	ND	ND	Yes	No
Abraham et al[49]	65/M	UC	4.8 g	2 wk	T, D, DC9	No	I	LP/IF	ND	ND	ND	Yes	No
Kim et al[50]	30/F	UC	1 g IR	19 d	PC	Yes 24%	I	EP	ND	Mo: 73% N: 19%	ND	Yes	No
Michy et al[12]	72/M	UC	ND	4 mo	D	Yes	ND	EP	ND	L: 23% N: 28% E: 14%	ND	Yes	Yes/No10
Current case	32/M	UC	1.5-3 g3	14 mo	T, D, DC, CP	Yes 62%	I	EP	CD4: 29% CD8: 56% Ratio: 0.51	E: 72%	67%	Yes	No

¹Time under mesalazine treatment before symptoms appeared;

²Patient was on low-dose Deflazacort during all the course of the pulmonary disease;

³Mesalazine dose was increased after patient was admitted;

⁴Bilateral pleural effusion was also noted;

⁵Patient improved after reducing mesalazine dose;

⁶Rechallenge was intended with olsalazine 1.5 g/d, with no recurrence;

⁷Patient had no response to glucocorticoid therapy but showed improvement after mesalazine withdrawal;

⁸After mesalazine removal a second rechallenge with sulfasalazine was intended with no recurrence of symptoms;

⁹Patient required endotracheal intubation for severe respiratory insufficiency;

¹⁰No recurrence was noted after the reintroduction of mesalazine enemas. A: Alveolar pattern; B: Bronchiectasis; BAL: Bronchoalveolar lavage; BO: Bronchiolitis obliterans; CD: Crohn’s disease; CP: Chest pain; CT: Corticoid therapy; D: Dyspnea; DC: Dry cough; DLCO: Diffusion capacity for carbon monoxide; E: Eosinophils; EOS: Eosinophilia; EP: Eosinophilic pneumonia; F: Female; HF: Histopathologic findings; I: Interstitial pattern; IF: Interstitial fibrosis; IP: Interstitial pneumonitis; IR: Intrarectal; L: Lymphocytes; LP: Lymphocytic pneumonitis; M: Male; Mo: Monocytes; N: Neutrophils; N/A: Not applicable; NC: No change; ND: No data available; NL: Normal; PC: Productive cough; PE: Pleural effusion; R: Rash; RP: Radiologic pattern; T: Fever; UC: Ulcerative colitis.

Table 2 Summary of previously published cases of mesalazine-induced cardiac hypersensitivity in patients with inflammatory bowel disease

Ref.	Age (yr)/sex	Disease	Daily dose	Duration of therapy	Symptoms	Cardiac disease	Pharmacologic treatment	Rechallenge /recurrence
Vayre et al[51]	53/M	CD	500 mg	8 yr	T, CP	AP, PE	Prednisolone	No
Ishikawa et al[16]	17/M	UC	1.5 g	2 wk	T, CP	AP, PE	Prednisolone	Yes/Yes
Doganay et al[52]	21/M	UC	2 g	10 d	T, D	AM	Budesonide	No
García-Morán et al[17]	39/M	UC	4 g P.O. + 2 g (enemas)	2 d	T, CP	AM, AMI	Methylprednisolone	No
Martín et al[53]	22/M	UC	3 g	ND	CP	AM	Corticosteroids	No
Cappell et al[15]	32/M	UC	ND	10 yr	T, CP, D	Chronic pericarditis, PT	Prednisone	No
Bernal-Sprekelsen et al[54]	54/M	UC	1.5 g	3 wk	T, CP	AP, PE	ASA	Yes/Yes1
Freeman et al[55]	26/M	UC	1.6 g	3 wk	T, CP	AM	Hydrocortisone	Yes/No2
Sierra Ausín et al[56]	47/M	UC	3 g P.O. + 1 g (enemas)	3 wk	T, CP	AP	NSAIDs	No
Park et al[57]	26/M	UC	2.4 g	1 mo	T, CP	AM, PE	ASA, prednisolone	Yes/Yes
Calafat et al[13]	37/M	UC	1 g IR	1 mo	CP	AP, PE	ASA	No
	37/F	UC	3g	2 wk	CP	AP, PE	Analgesics	No
Sonu et al[58]	20/F	UC	Sulfasalazine 2 g + mesalazine (enemas)3	3 wk	CP	AM, PT	Ibuprofen and colchicine	Yes/Yes4
Current case	32/M	UC	1.5-3 g5	14 mo	T, CP, D	AP, PE	Prednisone	No

¹After mesalazine suspension a rechallenge with mesalazine 500 mg IR was intended with recurrence of symptoms;

²After mesalazine suspension a rechallenge with sulfasalazine was intended without recurrence of symptoms;

³Mesalazine dose was not specified;

⁴After both sulfasalazine and mesalazine enemas were suspended, and low-dose balsalazide was initiated with recurrence of symptoms;

⁵Mesalazine dose was increased after patient was admitted. AP: Acute pericarditis; AM: Acute myopericarditis; AMI: Acute mitral insufficiency; ASA: Acetylsalicylic acid; CD: Crohn’s disease; CP: Chest pain; D: Dyspnea; F: Female; IR: Intrarectal; M: Male; ND: No data available; NSAIDs: Nonsteroidal anti-inflammatory drugs; PE: Pericardial effusion; PT: Pericardial tamponade; T: Fever; UC: Ulcerative colitis.