Cytapheresis for pyoderma gangrenosum associated with inflammatory bowel disease: A review of current status

Table 1 Clinical characteristics of cases treated with cytapheresis

Case (number)	Ref.	First authors	Reporting year	Age (yr)	Gender	The site of PG	Associated disease	Treatment before apheresis
1	[8]	Ohmori T	2003	19	M	Buttocks and legs	CD	5-ASA
2	[14]	Ishikawa H	2004	30	M	Abdomen, right iliac	UC	GC, CsA
3	[15]	Murata M	2004	31	M	Right lower leg	UC	GC
4	[16]	Yoneda K	2005	39	F	Face and head	UC	GC
5	[17]	Yanar-Fujisawa R	2005	31	F	Left ankle and right knee	UC	GC
6	[20]	Seishima M	2007	29	F	Lower bilateral legs	UC	GC, SASP
7	[21]	Fujino Y	2008	55	F	Lower bilateral legs	UC	GC, 5-ASA
8	[22]	Kawakami T	2009	19	M	Head	UC	GC, SASP
9	[23]	Doi R	2010	19	M	Forehead	UC	GC, SASP
10	[24]	Kobayashi S	2011	29	M	Right lower leg	UC	GC, SASP
11	[25]	Ikeda K	2011	36	F	Lower leg, neck and upper trunk	UC	GC
12	[26]	Uchiyama K	2011	50	F	Lower limbs	UC	GC
13	[27]	Urushibara M	2014	44	F	Back, left leg	UC	GC, 5-ASA, FK506
14	[28]	Izaki S	2014	49	F	Forearms	UC	SASP, PI
15	[29]	Ohno M	2016	36	F	Lower limbs	UC	SASP
16	[31]	Okada M	2017	71	F	Buttocks	UC	GC, 5-ASA
17	[32]	Yamashita A	2017	30	F	Top of the foot	UC	5-ASA
18	NA	Our Case	2018	57	M	Left lower leg	UC	GC, 5-ASA
19	[33]	Murata M	2003	19	F	Lower left leg	UC	GC
20	[34]	Fujimoto E	2004	42	M	Legs	UC	GC, SASP
21	[35]	Watanabe Y	2008	60	F	Left dorsal femur	UC	GC, DDS, CsA
22	[36]	Hanafusa T	2011	73	F	Sternum and chest	IBD, breast cancer	GC, DDS, CsA
23	[37]	Ito A	2015	43	F	Lower left leg	UC	GC, SASP

M: Male; F: Female; IBD: Inflammatory bowel disease; CD: Crohn's disease; UC: Ulcerative colitis; RA: rheumatoid arthritis; MDS: Myelodysplastic syndromes; GC: Glucocorticoid; SASP: Salazosulfapyridine; 5-ASA: 5-aminosalicylic acid; CsA: Cyclosporine; PI, potassium iodide; DDS: Diamino diphenyl sulfone; NA: Not available.

Table 2 Clinical course of the cases

Case (number)	Type of apheresis	Ulcer before the treatment	Number of therapies	CRP mg / dL (before, after)	WBC / μL (before, after)	Neutrophils % (before, after)	Clinical courses	Side effect	Relapse (follow up)
1	GCAP	NA	10	19.9, 0.6	17900, 4700	NA	Ulcer was fully re-epithelialized after 10 weeks	NA	NA
2	GCAP	NA	5	2.91, negative	NA	NA	Complete healing after 5th treatment	Mild headache	Yes (5 mo)
3	GCAP	NA	5	NA	NA	NA	Improve after 5th treatment	NA	NA
4	GCAP	NA	NA	NA	NA	NA	Symptoms were relieved with frequent GCAP and granulo-cytopenic therapy	NA	-
5	GCAP	NA	5	NA	NA	NA	Complete healing after 5th treatment	NA	-
6	GCAP	9 cm	10	NA	NA	NA	Pain relieved 2nd treatment; ulcers were re-epithelialized after 4th treatment	None	-
7	GCAP	NA	10	7.1, negative	NA	NA	Ulcer was fully re-epithelialized after 9th treatment	NA	-
8	GCAP	NA	NA	NA	NA	NA	Complete healing after the treatment	NA	-
9	GCAP	NA	11	NA	NA	NA	Ulcer was fully re-epithelialized one month after the 1st treatment	NA	-
10	GCAP	NA	5	NA	NA	NA	Ulcer improved partly but remained	NA	Yes (2 mo)
11	GCAP	7 cm	5	13.71, 0.21	NA	NA	Ulcer improved after 5th treatment	None	No (6 mo)
12	GCAP	6.5 cm	10	NA	NA	NA	Ulcer was fully re-epithelialized 3 month after the 10th treatment	NA	Yes (6 mo)
13	GCAP	NA	10	12.1, negative	NA	NA	Ulcer was fully re-epithelialized after the 10th treatment	NA	-
14	GCAP	NA	5	NA	NA	NA	Ulcer improved 2 months after the 5th treatment	NA	2 times (1 mo, 2 mo)
15	GCAP	NA	10	6.53, negative	NA	NA	Ulcer and symptoms improved after 3rd treatment	None	-
16	GCAP	3.1 cm	10	NA	NA	NA	Ulcer was fully re-epithelialized 2 months after the 1st treatment	None	No (2 yr)
17	GCAP	NA	10	4.73, negative	NA	NA	Ulcer was fully re-epithelialized after the 10th treatment	NA	-
18	GCAP	7 cm	10	0.45, 0.04	12310, 7490	74.9, 89.0	Ulcer was partly re-epithelialized after the 10th treatment	None	No (4 yr)
19	LCAP	NA	5	7.76, negative	NA	NA	Ulcer was partly re-epithelialized after the 3rd treatment	NA	-
20	LCAP	NA	5	1.3, 0.3	10400, 6400	88, 60	Ulcer was fully re-epithelialized after the 3rd treatment	None	No (4 mo)
21	LCAP	4 cm	4	6.6, 0.1	10800, 9100	84, 90	Skin lesion improved 3 months after the 4th treatment	NA	-
22	LCAP	7 cm	10	4.7, 1.3	11900, 7140	NA	Ulcer was fully re-epithelialized after the first round of LCAP, recurred with the tapering of PSL during the 2nd period of LCAP.	NA	No (2 yr)
23	LCAP	NA	10	22.46, negative	NA	NA	Ulcer and symptoms improved after 10th treatment	NA	No

GCAP: Granulocytapheresis; LCAP: Leukocytapheresis; CRP: C-reactive protein; WBC: White blood cell; NA: Data not available

Table 3 Summary of cytapheresis

Treatment	Adsorbent	Blood volume	Common mechanism	Advantages/ features	Diseases	Contrain-dications	Major adverse events reported
GCAP/GMA	Cellulose acetate	1.5-2.0 L	Mobilization of naive leukocytes by activated leukocyte removal; Inhibition of Cellular Invasion of Activated Leukocytes; Suppression of inflammatory cytokines, increase of anti-inflammatory cytokines	High specificity for removing WBCs. 30%-50% removal of granulocytes and monocytes, and approximately 6% removal of lymphocytes	Ulcerative colitis; Crohn's disease; Pustular psoriasis; Pyoderma Gangrenosum	Granulocyte < 2000/mm3 associated with infection	Allergic symptoms; Nausea; Fever; Aabdominal oppression; Headache
LCAP	Polyethylene-telephthalate	2.0-4.0 L		High efficiency for removing WBCs Almost all granulocytes and monocytes, and 40%-60% of lymphocytes and platelets can be removedIncrease of naive T cells can be seen and its therapeutic effect can be expected by suppressing antibody production and immune reaction	Ulcerative colitis; Rheumatoid arthritis	Treatment with angiotensin-converting enzyme inhibitors

GCAP: Granulocytapheresis; LCAP: Leukocytapheresis; WBC: White blood cell.