Cutaneous allergic reaction to subcutaneous vitamin K1: A case report and review of literature

Table 2 Details of case reports of reactions to vitamin K1 (eczematous type)

First author	Country	Date	Sex	Age (yr)	Adm.	Dose (mg)	Onset	Reaction	Patch	I.c.	Other assessments	Comments	Outcome
								Location/duration
Piguet et al[17]	France	1964	F	33	IM		Before surgery	Buttock/wk	K1-	K1+		Alcoholic cirrhosis
					IM			Buttock, chest, face/8 d
Barnes et al[18]	United Kingdom	1976	F	31	IM	10	2 wk	Buttock/2 mo	ND	K1+	Biopsy	Budd–Chiari syndrome, PCV	Plaques disappeared
			F	30	IM	100	Several weeks	Upper arm, thigh/2 mo				Drug overdose, renal failure, generalized rash
Heydenreich et al[19]	Denmark	1977	F	51	IV	20 daily	8–10 d	Arms	K1+1	K1+	ST	Hepatitis, RA, GN	No skin problems
											Intracutaneous test, epicutaneous test
Bullen et al[20]	United Kingdom	1978	F	17	INJ	340	13 d	Buttock/11 d	ND	K1+, K4-1	Biopsy	CAH	Resolution with scaling
			F	24	INJ	360	9 d	Buttock/9 d	ND	K1+, K4-	Biopsy	CAH
			F	39	INJ	270	9 d	Buttock/19 d	ND	K1+, K4-	Biopsy	CAH, RA
			F	50	INJ	440	16 d	Buttock/18 d	ND	ND	Biopsy	CAH, liver congestion, RA
			F	48	INJ	300	10 d	Buttock/22 d	ND	K1+, K4-		Alcoholic cirrhosis
			F	12	INJ	280	7 d	Buttock/9 d	ND	K1+, K4-	Biopsy	Congenital hepatic failure
Robison et al[21]	United States	1978	M	63	IM	30	10 d	Upper arm	K1+1	K1+1	Biopsy	Alcoholic cirrhosis	Temporarily alleviated
											Epicutaneous test
Jean-Pastor et al[22]	France	1981+
Finkelstein et al[23]	Canada	1987	F	26	SC	280	11 d	Months	K1-, K3-	K1+, K3-	Biopsy	Metastatic cholangiocarcinoma	Hyperpigmentation remained
			F	42	SC	40	14 d	Months	K1+, K3-	ND	Biopsy	Primary biliary cirrhosis	Total bilirubin remained elevated
			F	39	IM	1750	2 d	Months	K1-, K3-	K1+, K3-	Biopsy	Chronic myeloid leukemia	Residual erythema scaling, pruritus, and hyperpigmentation
			M	51	SC	10	14 d	Months	K1+, K3-	K1+, K3-	Biopsy	Amyloidosis	Mild improvement
			F	64	SC	10	5 d	Months	K1+, K3-	ND	Biopsy	Cardiac cirrhosis	Persistent pruritus
			F	32	SC	10	14 d	Months	K1-, K3-	K1+, K3-	Biopsy	Preeclampsia with DIC
Joyce et al[24]	United States	1988	F	36	IM	20	14 d	Right arm/4 yr			Biopsy	Long-term warfarin therapy	Intermittent pruritus and persistent induration
			F	61	IM	10	6 d	Left arm/6 mo			Biopsy	Severe cardiac disease	Skin lesion persisted unchanged
												No significant medical abnormalities
Sanders et al[25]	United States	1988	F	18	SC	100	> 10 d	Buttock, upper arm/weeks		K1+, K4-	Biopsy	Anorexia, N/V	Lesions resolved
			F	28	SC	10	2 wk	Arm/1 mo		K1+, K4-		Dilated cardiomyopathy	Slowly resolved
			F	31	SC		10 d	Upper arm/2 wk				Healthy
			F	25	SC	40	After the injection	Weeks		K1+, K4-	Biopsy	Drug overdose, elevated LFT results	Rash cleared
Pigatto et al[26]	Italy	1990	F	9	IM		10 d	Buttocks	K1+, K2-, K3-			Minor beta thalassemia	Some residual pigmentation
												Factor X deficiency
Lee et al[27]	United States	1992	F	49	SC	110	During treatment	Upper arms, thighs, and buttocks/2 mo			Biopsy	CAH, variceal bleeds	Total regression of lesions
Tuppal et al[28]	Canada	1992	M	45	SC	330	Few days	Upper arms and abdomen/2 mo			Biopsy	Long history of ethanol abuse	Resolution of skin eruption
Lemlich et al[29]	United States	1993	F	43		30	2 wk	6 mo			Biopsy	Budd–Chiari syndrome, PCV	No sclerodermatous changes
			F	62		20	2 wk	1 mo			Biopsy	Stage Ⅳ endometrial carcinoma	Mild postinflammatory hyperpigmentation remained
			F	57			2 wk	Right arm/1 mo			Biopsy	Stage Ⅱ ovarian cancer
			F	50			2 wk	Left upper arm			Biopsy	Healthy	Remained symptomatic
Bruynzeel et al[30]	Netherlands	1995	F	32	SC		2 wk	Right upper arm/2 mo	K1-, K-	K+	Biopsy	Pelvic vein thrombosis	Resolution
			F	44	SC		4 wk	Left upper leg/mo				Acute pancreatic Ascaris lumbricoides infection	Lesion persisted
Balato et al[31]	Italy	1998	F	49	IM	30		Right buttock/4 mo	K-	K+	Biopsy		Lesion healed spontaneously
											Scratch-patch test
											Prick test
Wong et al[32]	Australia	1999	F	40	IM	40	5 d	Thighs/mo	K1+, K3+	K1+		Cholelithiasis, asthma, duodenal ulcer, and esophagitis	Residual erythema persisted
Wilkins et al[33]	Canada	2000	F	50	SC	15	1 wk	Left arm/18 mo			Biopsy	Hypothyroidism, superficial phlebitis	Eruption persisted with occasional flares
Sommer et al[34]	United Kingdom	2002	F	27	IM		1 d	Thigh/2 yr	K1+, K4+			CF, CF-related DM	Symptoms persisted
Bui et al[35]	United States	2004	F	21	SC	65	10 d	Arms, abdomen/19 d				N/V, Wilson’s disease	Rash disappeared
Giménez-Arnau et al[36]	Spain	2005	F	64	IM		1 wk	Buttock	K1-	K1+	Biopsy	Chronic hepatitis C virus liver disease	Skin healed
											Immunoallergic study
											Prick test
Our case	China	2022	F	50	SC	40	5 d	Right hip			Biopsy	Multiple thyroid nodules	A few residual pigments in the lesion area and no itching sensation
											IHC

¹Patch or intracutaneous tests performed in controls.

+Six patients were reported as “personal observations” but no details were provided for individual patients.

CAH: Chronic active hepatitis; DIC: Disseminated intravascular coagulation; DM: Diabetes mellitus; GN: Glomerulonephritis; LFT: Liver function test; N/V: Nausea and vomiting; PCV: Polycythemia vera; RA: Rheumatoid arthritis; SLE: Systemic lupus erythematosus; CF: Cystic fibrosis; INJ: Injection; IHC: Immunohistochemical; Adm.: Administration; SC: Subcutaneous; IM: Intramuscular; IV: Intravenous; ND: No allergy tests performed; ST: Scratch test; Patch test: 2-4 d; Intracutaneous test: 1-4 d.