High Baseline C-Reactive Protein Level Can Predict the Occurrence of the Jarisch–Herxheimer Reaction in Patients with Active Syphilis

Figures & data

Table 1 Demographic Data of the 29 Patients with Syphilis

Parameters		Patient Number (%) N=29
Gender	Male	29 (100)
Age (years)	Median	30
	IQR	25–37
Risk factor	MSM	29 (100)
HIV co-infection	No	8 (27.6)
	Yes	21 (72.4)
HIV viral load (copies/mL) at enrollment (N=21)	Median	<20
	IQR	<20–18,966
CD4 count at enrollment (N=21)	Median	526
	IQR	310–707
RPR titer before treatment	Median	1:128
	IQR	1:64–1:256
Syphilis episode	First episode	14 (48.3)
	≥2	15 (51.7)
Treatment of syphilis (benzathine penicillin 2.4 mu)	1 shot	16 (55.2)
	2 shots	1 (3.4)
	3 shots	12 (41.4)
Time (hours) from treatment to blood sampling for evaluation of the JHR	Median	3.58
	IQR	2.35–4.16
JHR after benzathine penicillin treatment	Negative	17 (58.6)
	Positive	12 (41.4)
Time (hours) from treatment to development of the JHR	Median	5
	IQR	3.5–7.2
JHR in patients with a first episode of syphilis (N=14)	Negative	7 (50)
	Positive	7 (50)
JHR in patients with recurrent syphilis (N=15)	Negative	10 (66.7)
	Positive	5 (33.3)
RPR titer decreased at least 4-fold after 1 year (N=25)	YES	21 (84)
	NO	4 (16)

Abbreviations: HIV, human immunodeficiency virus; RPR, rapid plasma reagin; IQR, interquartile range; MSM, men who have sex with men; JHR, Jarisch-Herxheimer reaction.

Table 2 Clinical Manifestations of 12 Syphilitic Patients with the Jarisch-Herxheimer Reaction After Benzathine Penicillin Treatment

Parameters	Frequency (%)
Fever	10 (83)
Exacerbated skin rash	9 (75)
Chills	2 (17)
Dizziness/headache	4 (33)
Weakness	1 (8)
Myalgia	1 (8)

Table 3 Baseline CRP Levels of the 29 Patients with Active Syphilis and Three Control Groups

	HIV-Syphilis- N=10	HIV+Syphilis- N=10	HIV+Syphilis+ N=12	Active Syphilis N=29	Kruskal–Wallis Test (p-value)
CRP
Median	460.3	1391.2	739.6	11,761.0	<0.0001
IQR	123–1674	254–2286	394–1412	2986–19,061

Abbreviations: HIV, human immunodeficiency virus; IQR, interquartile range; CRP, C-reactive protein.

Table 4 Changes in Serum CRP Levels Among Syphilitic Patients with and without the JHR After Benzathine Penicillin Treatment

	No JHR Before Treatment	JHR Before Treatment	Mann–Whitney U-Test (p-value) 95% CI	No JHR After Treatment	JHR After Treatment	Mann–Whitney U-Test (p-value) 95% CI
All syphilitic patients (N=29)
	N=17	N=12		N=17	N=12
CRP
Median	3488.6	16,262	0.0059	4328	16,159	0.0051
IQR	924–16,064	12,032–26,150	4002 ~ 17,098	482–13,328	9352–24,561	3954 ~ 17,401
HIV-infected syphilitic patients (N=21)
	N=14	N=7		N=14	N=7
CRP
Median	3280.2	14,953.6	0.0556	3712.6	18,131.4	0.0309
IQR	1080–18,732	11,761–27,160	−1808 ~ 17,637	527–15,555	9003–25,183	667 ~ 20,300

Abbreviations: CRP, C-reactive protein; JHR, Jarisch-Herxheimer reaction; IQR, interquartile range; HIV, human immunodeficiency virus.

Table 5 Changes in Serum CRP Levels Before and After Benzathine Penicillin Treatment Among Syphilitic Patients with and without the JHR

	No JHR Before Treatment N=17	No JHR After Treatment N=17	Wilcoxon Signed Rank Test (p-value) 95% CI	JHR Before Treatment N=12	JHR After Treatment N=12	Wilcoxon Signed Rank Test (p-value) 95% CI
CRP
Median	3488.6	4328	0.7467	16,262	16,159	0.3013
IQR	924–16,064	482–13,328	−851 ~ 817	12,032–26,150	9352–24,561	−3162 ~ 1341

Abbreviations: CRP, C-reactive protein; JHR, Jarisch-Herxheimer reaction; IQR, interquartile range.

Table 6 Serum Baseline CRP Levels Prior to Treatment Between HIV Infection, Different RPR Titer, Syphilis Stage and JHR

Parameter	Negative	Positive	M-W U-Test (p-value) 95% CI
HIV	N=8	N=21
Median	11,457	11,761	0.754
IQR	5189–21,732	2281–19,061	−11,186 ~ 8493
RPR≦32	N=4	N=25
Median	18,222	7050	0.1416
IQR	14,028–25,089	2281–18,905	−17,451 ~ 4245
RPR≦64	N=10	N=19
Median	18,065	7050	0.2461
IQR	3775–20,671	1237–14,954	−14,498 ~ 4148
RPR≦128	N=18	N=11
Median	13,936	3489	0.1312
IQR	4443–20,217	472–14,954	−14,304 to 1828
RPR≦256	N=24	N=5
Median	11,457	11,761	0.9326
IQR	2944–19,155	2442–26,299	−12,533 to 12,709
JHR with fever or skin rash	N=17	N=12
Median	3489	16,262	0.0059
IQR	924–16,064	12,033–26,150	4002 to 17,098
JHR to fever	N=19	N=10
Median	4066	16,914	0.0057
IQR	1237–17,570	12,576–27,213	6002 to 18,560
JHR with skin rash	N=20	N=9
Median	4317	17,570	0.0264
IQR	1343–17,496	11,457–25,245	650 to 16,958
Syphilis stage	N=7 (primary syphilis)	N=22 (secondary syphilis)
Median	2901	13,208	0.1428
IQR	1237–19,249	4443–19,935	−1818 to 15,385

Abbreviations: HIV, human immunodeficiency virus; RPR, rapid plasma reagin; IQR, interquartile range; JHR, Jarisch-Herxheimer reaction; CRP, C-reactive protein.

Figure 1 Baseline CRP levels among 29 patients with active syphilis and three control groups. **P< 0.01; ***P< 0.001.

Abbreviations: HIV- Syphilis-, men who have sex with men (MSM) who were taking pre-exposure prophylaxis (PrEP) and did not have HIV or syphilis infection; HIV+ Syphilis-, HIV-infected patients without syphilis; HIV+ Syphilis+, HIV-infected patients with previous syphilis.

Figure 2 Changes in serum CRP levels before and after benzathine penicillin treatment among 12 syphilitic patients with the JHR and 17 without the JHR. **P< 0.01.

Abbreviations: JHR, Jarisch–Herxheimer reaction; BE, before benzathine penicillin treatment; AF, after benzathine penicillin treatment.

Figure 3 Changes in serum CRP levels among 7 HIV-infected syphilitic patients with the JHR and 14 HIV-infected syphilitic patients without the JHR after benzathine penicillin treatment. *P< 0.05.

Abbreviations: JHR, Jarisch–Herxheimer reaction; BE, before benzathine penicillin treatment; AF, after benzathine penicillin treatment.

Figure 4 Changes in serum CRP levels before and after benzathine penicillin treatment among 12 syphilitic patients with the JHR and 17 without the JHR.

Abbreviations: JHR, Jarisch–Herxheimer reaction; BE, before benzathine penicillin treatment; AF, after benzathine penicillin treatment.

Figure 5 ROC curve for serum CRP to differentiate the occurrence of the JHR among 29 syphilitic patients treated with benzathine penicillin.