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

Table 1 Details of the decoction for blood cooling and Yang restraining (translated in English)

Main composition	Chinese pinyin	Latin scientific name	Medicinal source	Crude drug content (g)
Radix Cyathulae	Chuan Niu Xi	Cyathula officinalis Kuan	Root	12
Rhizoma Alismatis	Ze Xie	Alisma plantago-aquatica L	Tuber	12
Belvedere fruit	Di Fu Zi	Fructus Kochiae	Fruit	15
Cortex	Bai Xian Pi	Cortex dictamni	Root bark	12
Mother of pearl	Zhen Zhu Mu	Concha Margaritifera Usta	Shell	30
Magnetite	Ci Shi	Magnetium	Fe3O4	30
Liquorice	Gan Cao	Glycyrrhiza uralensis Fisch	Root	3
Herba Lycopi	Ze Lan	Aconitum gymnandrum Maxim	Leaf	9
Scutellaria baicalensis	Huang Qin	Scutellaria baicalensis Georgi	Root	12
Rehmannia	Di Huang	Rehmannia glutinosa	Root	15
Prepared rehmannia	Shu Di Huang	Rehmannia glutinosa	Root	15
Cortex Moutan	Mu Dan Pi	Cortex Moutan Radicis	Root bark	12
Red-rooted Salvia	Sheng Dan Shen	Salvia miltiorrhiza Bge	Root	15
Red peony	Chi Shao	Radix Paeoniae Rubra	Root	12
Sophorae Flavescentis	Ku Shen	Sophora flavescens	Root	12
Angelicae Sinensis	Guan Huang Bai	Phellodendron amurense Rupr	Bark	12

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.