Case Report Open Access
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 16, 2022; 10(29): 10742-10754
Published online Oct 16, 2022. doi: 10.12998/wjcc.v10.i29.10742
Cutaneous allergic reaction to subcutaneous vitamin K1: A case report and review of literature
Miao Zhang, Chun-Xiao Wang, Nai-Xuan Lin, Xin Li, Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
Miao Zhang, Chun-Xiao Wang, Nai-Xuan Lin, Xin Li, Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China
Jia Chen, Department of Dermatopathology, Shanghai Skin Disease Hospital, Tongji University, Shanghai 200443, China
ORCID number: Miao Zhang (0000-0002-0340-2043); Jia Chen (0000-0002-7094-9460); Chun-Xiao Wang (0000-0002-5233-9079); Nai-Xuan Lin (0000-0002-6754-4606); Xin Li (0000-0003-2525-9679).
Author contributions: Zhang M contributed to the manuscript writing and editing and the data collection; Chen J, Wang CX, and Lin NX contributed to the data analysis; Li X contributed to the study conceptualization and supervision; all authors have read and approved the final manuscript.
Informed consent statement: Written informed consent was obtained from the patient for the publication of this case and accompanying images.
Conflict-of-interest statement: The authors declare no conflicts of interest related to the publication of this report.
CARE Checklist (2016) statement: The authors read the CARE Checklist (2016) and prepared and revised the manuscript accordingly.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xin Li, MD, PhD, Director, Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Shanghai 200437, China.
Received: May 31, 2022
Peer-review started: May 31, 2022
First decision: June 27, 2022
Revised: July 9, 2022
Accepted: August 23, 2022
Article in press: August 23, 2022
Published online: October 16, 2022


Vitamin K1 (phytomenadione) is a fat-soluble naturally occurring vitamin that is widely used to treat certain coagulation disorders. Adverse cutaneous reactions to vitamin K1 can occur; however, owing to its low incidence and considerable variability in presentation and morphology, its diagnosis can be easily overlooked. Managing these reactions may be challenging for patients and clinicians. Therefore, reviewing the adverse cutaneous reactions to vitamin K1 is important.


Here we report the case of a 50-year-old woman with no pre-existing hepatic disease who developed a cutaneous allergic reaction to subcutaneous vitamin K1 that presented as localized eczematous plaques at the vitamin K1 injection site. The eruption developed within 5 d of the injection and persisted for 32 mo despite treatment with topical and intralesional steroids. Eczema was diagnosed based on the results of the pathological examination, immunohistochemical staining, and a skin biopsy. The patient was advised to take herbal medicines orally twice daily. After treatment and follow-up, the patient’s eczematous urticarial plaques improved and her condition stabilized.


Here we present the first case of a cutaneous allergic reaction to subcutaneous vitamin K1 that was successfully treated with Chinese medicine.

Key Words: Vitamin K1 , Subcutaneous injection, Adverse reactions, Herbal medicine, Polyoxyethylated castor oil, Case report guidelines, Case report

Core Tip: Adverse cutaneous reactions to vitamin K1 can occur; however, their diagnosis can easily be overlooked. Managing these reactions may be challenging for both patients and clinicians. Here we report a patient who developed a cutaneous allergic reaction to subcutaneous vitamin K1 that was successfully treated with herbal medicine, suggesting that Chinese medicine therapy may be a feasible way to treat adverse cutaneous reactions. We confirmed our clinical findings through physical examination, a skin biopsy, and immunohistochemical staining. We also conducted a literature review of eczematous-type reactions to clarify the possible pathogenesis and provoke new thinking regarding the clinical treatment of this disease.


Vitamin K1, currently available for oral, intramuscular, subcutaneous, or intravenous administration, is generally well tolerated[1]. However, adverse effects of vitamin K1 have rarely been observed and were mostly reported in the early 1960s in the European literature. The most important adverse effects of vitamin K1 are hyperbilirubinemia and kernicterus in newborn infants[2], particularly in premature infants resulting from the competition for glucuronyl transferase in the presence of immature liver function[3].

Based on to the characteristics of skin rashes, three types of adverse events can be caused by vitamin K1 injection: (1) Localized pruritic erythematous, eczematous, indurated plaques (most common); (2) localized morphea-form eruptions (secondary to the eczematous type[4-8]); and (3) diffuse maculopapular eruptions (very rare), which were reported in early studies[9-11]. In accordance with the case report guidelines[12], here we present a case of a patient who developed an eczematous-type reaction to vitamin K1 injection. Residual pigmentation persisted after 18 mo of treatment; however, the patient responded well to treatment with Chinese medicine (CM).

Cutaneous reactions caused by vitamin K1 injections are mainly treated symptomatically. Most patients are treated with topical corticosteroids with or without occlusion and intralesional steroids; however, these treatments are ineffective. The topical application of tacrolimus (FK-506), a potent interleukin-2 and T-cell activation inhibitor, may become a future treatment option. Lauerma[13] demonstrated that topical tacrolimus pretreatment effectively suppresses allergic contact dermatitis caused by dinitrobutylphenol. However, its use for treating cutaneous hypersensitivity reactions to vitamin K1 has not been reported.

Some researchers believe that the exacerbation of persistent eruptions may be related to dietary vitamin K. However, no follow-up investigation of this possibility is available in the English literature. This is probably due to difficulty avoiding dietary vitamin K1, as small quantities are present in many different foods, with high concentrations in green leafy vegetables. Our patient failed to maintain a low vitamin K1 diet due to food preferences. Hence, whether the minute quantities of vitamin K1 present in some foods preclude the efficacy of dietary therapy remains unknown.

Chief complaints

A 50-year-old woman was referred to our hospital on September 14, 2020 with the complaint of an intensely pruritic erythematous patch on her right hip.

History of present illness

The patient’s symptom of an intensely pruritic erythematous patch started 1 year before presentation.

History of past illness

One year prior, the patient had received subcutaneous injections of vitamin K1 40 mg before thyroid nodule surgery to prevent bleeding. Five days after the injections, she developed the abovementioned symptoms at the injection site that caused discomfort without any obvious burning, pain, or other problems. She had not been treated with phytonadione, cyclosporine, or other medications containing polyoxyethylated castor oil (PEO-CO). She was diagnosed with urticaria, for which topical chloramphenicol betamethasone liniment, dexamethasone sodium phosphate, and chlorpheniramine maleate injections were prescribed. However, her condition did not improve substantially. Despite intermittent treatment for one year, her condition was not well controlled.

Personal and family history

The patient denied any family history of any hereditary disease.

Physical examination

A physical examination revealed an erythematous itchy-infiltrated area of approximately 10 cm × 10 cm on the right hip at the injection sites. The patient had a dry mouth, no sweat, and normal urine and bowel movements. Her tongue was red and covered with a thin and greasy coating, and her pulse was fine and rapid. Since the onset of the disease, she had no fever, chills, joint pain, swollen lymph nodes, weight loss, trauma, foreign body contact, or suspicious drug use. Her clinical symptoms of intense pruritus and weeping, erythematous, eczematous, and indurated plaques are shown in Figure 1A and B.

Figure 1
Figure 1 Clinical presentation and diagnostic clues from the original symptoms. A and B: Intensely pruritic, weeping, erythematous, eczematous, and indurated plaques; C: An intense perivascular infiltrate composed of lymphocytes and histiocytic cells, with rare plasma cells and eosinophils (hematoxylin–eosin stain, 100 ×); D: Prominent endothelial cell swelling. The infiltrate extended through the reticular dermis into the subcutaneous fat and focally surrounded the eccrine and neural structures (hematoxylin–eosin stain, 400 ×); E and F: The lower half of the dermis was markedly sclerotic with thickened eosinophilic collagen bundles. A microscopic examination revealed a normal epidermis and more lymphocytes infiltrating the blood vessels in the dermis, several of which were mimicking Pautrier microabscesses (100 ×).
Laboratory examinations

Liver ultrasonography findings and aspartate aminotransferase (serum glutamic oxaloacetic transaminase), alkaline phosphatase, and serum bilirubin levels were normal.

Skin biopsy

A clear diagnosis of the disease could not be made based on the clinical manifestations of the erythematous and eczematous plaques. The patient’s skin lesions were nonspecific and could be easily confused with mycosis fungoides (MF). To ensure diagnostic accuracy, we performed a biopsy of the skin from the right hip during the examination, the results of which were available within a week. Considering the characteristics of the skin lesions, we temporarily suspected an adverse cutaneous reaction to vitamin K1 (eczematous type), and the CM diagnosis was “wet sores.” The tongue coating, pulse, and skin lesion characteristics were consistent with those of blood-heat syndrome. We considered blood heat and Yang floating as the main pathogeneses according to the CM theory.

Histological examination

The erythema area was reduced, the degree of itching was alleviated, and the patient’s condition gradually stabilized by November 12, 2020. The patient’s tongue was reddish with a white and greasy coating and her pulse was slippery. A skin biopsy was performed (Figure 1C and D), and a histological examination showed an intense perivascular infiltrate composed of lymphocytes and histiocytic cells with rare plasma cells and eosinophils. Prominent endothelial cell swelling was also observed. The infiltrate extended through the reticular dermis into the subcutaneous fat and focally surrounded the eccrine and neural structures. The lower half of the dermis was markedly sclerotic with thickened eosinophilic collagen bundles. These findings were consistent with our diagnosis.

Further diagnostic work-up

A microscopic examination revealed a normal epidermis and more lymphocytes infiltrating the blood vessels in the dermis, several of which mimicked Pautrier microabscesses (Figure 1E and F). Immunohistochemical (IHC) staining showed that T cells were positive for CD3, CD5, and CD4 and partially positive for CD8 (Figure 2A-D). B cells were positive for CD20 and CD79a (Figure 2E and F). Histocytes were positive for CD68, natural killer cells were positive for CD56, and mastocytes were negative for CD117 (Figure 3A-C). B cells tested positive for common acute lymphoblastic leukemia antigen (CD10), negative for platelet-endothelial cell adhesion molecule-1 was negative for (CD31), and negative for syndecan-1 (CD138) (Supplementary Figure 1). We ruled out MF because the IHC results suggested that the cells in this case were multi-lineage and polyclonal.

Figure 2
Figure 2 Immunohistochemical assay for positive phenotypes. A-D: T cells tested positive for CD3, CD5, and CD4 and partially positive for CD8 (200 ×); E and F: B cells tested positive for CD20 and CD79a (200 ×).
Figure 3
Figure 3 Immunohistochemical assays for other phenotypes. A-C: Histocytes were positive for CD68+, natural killer cells tested positive for CD56, and mastocytes tested negative for CD117 (200 ×).

According to the clinical picture, histopathology results, and IHC results, the final diagnosis was a cutaneous allergic reaction to the vitamin K1 injections.


The patient was treated with an oral herbal medicine for “cooling blood and restraining Yang” twice daily, 30 min after meals. Our team previously reported that blood-cooling and Yang-restraining herbs had a positive clinical effect in the treatment of skin diseases such as blood-heat syndrome, eczema, and psoriasis vulgaris[14,15]. Other authors showed that the drug for cooling blood and restraining Yang may upregulate the expressions of PD-1 mRNA, PD-L2 mRNA, and their proteins in patients with psoriasis vulgaris, which manifests as blood-heat syndrome[16]. The specific compositions, dosages, and medicinal sources of these herbal decoctions are listed in Table 1.

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 CyathulaeChuan Niu XiCyathula officinalis KuanRoot12
Rhizoma AlismatisZe XieAlisma plantago-aquatica LTuber12
Belvedere fruitDi Fu ZiFructus KochiaeFruit15
Cortex Bai Xian PiCortex dictamniRoot bark12
Mother of pearlZhen Zhu MuConcha Margaritifera UstaShell30
MagnetiteCi ShiMagnetiumFe3O430
LiquoriceGan CaoGlycyrrhiza uralensis FischRoot3
Herba LycopiZe LanAconitum gymnandrum MaximLeaf9
Scutellaria baicalensisHuang QinScutellaria baicalensis GeorgiRoot12
RehmanniaDi HuangRehmannia glutinosaRoot15
Prepared rehmanniaShu Di HuangRehmannia glutinosaRoot15
Cortex MoutanMu Dan PiCortex Moutan RadicisRoot bark12
Red-rooted SalviaSheng Dan ShenSalvia miltiorrhiza BgeRoot15
Red peonyChi ShaoRadix Paeoniae RubraRoot12
Sophorae FlavescentisKu ShenSophora flavescensRoot12
Angelicae SinensisGuan Huang BaiPhellodendron amurense RuprBark12

The previous misdiagnosis was corrected in a timely manner. Nevertheless, the main components of the blood-cooling and yang-restraining herbal medicine remained unchanged. The dose of the drug was adjusted appropriately, and the patient continued to reduce her intake of leafy green vegetables.

The patient was followed up on June 23, 2021, March 6, 2022, and April 2, 2022. After taking the herbal medicine, the patient’s erythema area was reduced, the degree of itching was alleviated, and her symptoms improved significantly. Her tongue was still red with a thin and greasy coating and her pulse was fine and rapid; hence, the composition of the herbal medicine was adjusted accordingly. After taking the herbal medicine for 18 mo, her symptoms greatly improved with only a few residual pigments in the lesion area and no itching sensation. She stopped taking the oral herbal medicine in April 2022 in accordance with the doctor’s advice.

At presentation, the patient showed some inconspicuous pigment residues with no itching sensation, and the lesions did not involve the internal organs or lymph nodes. Throughout the treatment and follow-up period, the patient showed good adherence to and tolerance of the CM therapy, and no adverse or unanticipated events occurred during this period. The patient’s condition was well controlled, and her quality of life improved. She was regularly followed up at a local clinic, with no complaints of discomfort or adverse events during treatment. At the 18-mo follow-up, the eczematous erythema plaques on her right hip had notably improved compared to the pretreatment condition. However, the eruption persisted with occasional pruritus for approximately 32 mo. The patients’ skin lesions before and after treatment are shown in Figure 4A and B. The full timeline of diagnosis, medical treatment process, physical examination findings, clinical characteristics, and laboratory findings are shown in Figure 5.

Figure 4
Figure 4 Clinical presentation before and after treatment. A: Appearance of the skin before treatment (September 14, 2021); B: Appearance of the skin during follow-up (March 6, 2022). In the 1.5 years follow-up period, the area of erythema was reduced, the degree of itching was alleviated, and the patient’s condition gradually stabilized.
Figure 5
Figure 5 Case timeline. Important dates, times, and detailed diagnostic process during the treatment and follow-up period.

Our patient developed severe localized reactions at the site of the subcutaneous injections of vitamin K1, and the lesions slowly subsided over a 32-mo period. Although the early changes resembled urticaria, they were not transient. Most importantly, the swollen red plaques involved underlying dermal involvement and epidermal changes. The diagnosis was confirmed by clinical imaging, histopathology, and IHC staining. The persistence of the pruritus in our patient may imply that the drug may have remained locally at the injection site or that an altered host tissue reaction in the skin may have provided a continued antigen stimulus.

We summarized the results of the 20 cases reported to date of eczematous-type reactions in Table 2, including the administration route, dose, reaction, and diagnostic assessment, with the aim of determining the pathogenesis of this hypersensitivity. Several features of the eczematous reaction to vitamin K1 suggest that it was a manifestation of delayed-type hypersensitivity, a prototype of type IV cell-mediated immunity. In most cases, lesions appeared approximately 7-10 d after the first dose of vitamin K1[17-36]. In addition, subsequent patch and intradermal testing produce a reaction within 3-5 and 1-2 d, respectively[17-21,23,25,26,31,32,34,36]. The time sequence of the development of these reactions corresponded well with type IV cell-mediated hypersensitivity. The positive results of sensitivity testing using patch test methods implied that sufficient antigens may have been absorbed to generate an immune response. Several patients exhibited a recall reaction[21,23,30] in previously affected areas compatible with the recall phenomenon in allergic contact eczema when antigens applied in new areas precipitate an eczematous flare-up. Several histopathological studies of biopsy specimens from the lesion and the intracutaneous test site showed spongiosis of the epidermis, dermal edema, and perivascular mononuclear and eosinophilic cellular infiltrates consistent with delayed-type hypersensitivity[18,20-25,27-31,33,36].

Table 2 Details of case reports of reactions to vitamin K1 (eczematous type).
First authorCountryDateSexAge (yr)Adm.Dose (mg)OnsetReaction
PatchI.c.         Other assessmentsCommentsOutcome
Piguet et al[17]France1964F33IMBefore surgeryButtock/wkK1-K1+Alcoholic cirrhosis
IMButtock, chest, face/8 d
Barnes et al[18]United Kingdom1976F31IM102 wkButtock/2 moNDK1+BiopsyBudd–Chiari syndrome, PCVPlaques disappeared
F30IM100Several weeksUpper arm, thigh/2 moDrug overdose, renal failure, generalized rash
Heydenreich et al[19]Denmark1977F51IV20 daily8–10 dArmsK1+1K1+STHepatitis, RA, GNNo skin problems
Intracutaneous test, epicutaneous test
Bullen et al[20]United Kingdom1978F17INJ34013 dButtock/11 dNDK1+, K4-1BiopsyCAHResolution with scaling
F24INJ3609 dButtock/9 dNDK1+, K4-BiopsyCAH
F39INJ2709 dButtock/19 dNDK1+, K4-BiopsyCAH, RA
F50INJ44016 dButtock/18 dNDNDBiopsyCAH, liver congestion, RA
F48INJ30010 dButtock/22 dNDK1+, K4-Alcoholic cirrhosis
F12INJ2807 dButtock/9 dNDK1+, K4-BiopsyCongenital hepatic failure
Robison et al[21]United States1978M63IM3010 dUpper armK1+1K1+1BiopsyAlcoholic cirrhosisTemporarily alleviated
Epicutaneous test
Jean-Pastor et al[22]France1981+
Finkelstein et al[23]Canada1987F26SC28011 dMonthsK1-, K3-K1+, K3-BiopsyMetastatic cholangiocarcinomaHyperpigmentation remained
F42SC4014 dMonthsK1+, K3-NDBiopsyPrimary biliary cirrhosisTotal bilirubin remained elevated
F39IM17502 dMonthsK1-, K3-K1+, K3-BiopsyChronic myeloid leukemiaResidual erythema scaling, pruritus, and hyperpigmentation
M51SC1014 dMonthsK1+, K3-K1+, K3-BiopsyAmyloidosisMild improvement
F64SC105 dMonthsK1+, K3-NDBiopsyCardiac cirrhosisPersistent pruritus
F32SC1014 dMonthsK1-, K3-K1+, K3-BiopsyPreeclampsia with DIC
Joyce et al[24]United States1988F36IM2014 dRight arm/4 yrBiopsyLong-term warfarin therapyIntermittent pruritus and persistent induration
F61IM106 dLeft arm/6 moBiopsySevere cardiac diseaseSkin lesion persisted unchanged
No significant medical abnormalities
Sanders et al[25]United States1988F18SC100> 10 dButtock, upper arm/weeksK1+, K4-BiopsyAnorexia, N/VLesions resolved
F28SC102 wkArm/1 moK1+, K4-Dilated cardiomyopathySlowly resolved
F31SC10 dUpper arm/2 wkHealthy
F25SC40After the injectionWeeksK1+, K4-BiopsyDrug overdose, elevated LFT resultsRash cleared
Pigatto et al[26]Italy1990F9IM10 dButtocksK1+, K2-, K3-Minor beta thalassemiaSome residual pigmentation
Factor X deficiency
Lee et al[27]United States1992F49SC110During treatmentUpper arms, thighs, and buttocks/2 moBiopsyCAH, variceal bleedsTotal regression of lesions
Tuppal et al[28]Canada1992M45SC330Few daysUpper arms and abdomen/2 moBiopsyLong history of ethanol abuseResolution of skin eruption
Lemlich et al[29]United States1993F43302 wk6 moBiopsyBudd–Chiari syndrome, PCVNo sclerodermatous changes
F62202 wk1 moBiopsyStage Ⅳ endometrial carcinomaMild postinflammatory hyperpigmentation remained
F572 wkRight arm/1 moBiopsyStage Ⅱ ovarian cancer
F502 wkLeft upper arm BiopsyHealthyRemained symptomatic
Bruynzeel et al[30]Netherlands1995F32SC2 wkRight upper arm/2 moK1-, K-K+BiopsyPelvic vein thrombosisResolution
F44SC4 wkLeft upper leg/moAcute pancreatic Ascaris lumbricoides infectionLesion persisted
Balato et al[31]Italy1998F49IM30Right buttock/4 moK-K+BiopsyLesion healed spontaneously
Scratch-patch test
Prick test
Wong et al[32]Australia1999F40IM405 dThighs/moK1+, K3+K1+Cholelithiasis, asthma, duodenal ulcer, and esophagitisResidual erythema persisted
Wilkins et al[33]Canada2000F50SC151 wkLeft arm/18 moBiopsyHypothyroidism, superficial phlebitisEruption persisted with occasional flares
Sommer et al[34]United Kingdom2002F27IM1 dThigh/2 yrK1+, K4+CF, CF-related DMSymptoms persisted
Bui et al[35]United States2004F21SC6510 dArms, abdomen/19 dN/V, Wilson’s diseaseRash disappeared
Giménez-Arnau et al[36]Spain2005F64IM1 wkButtockK1-K1+BiopsyChronic hepatitis C virus liver diseaseSkin healed
Immunoallergic study
Prick test
Our caseChina2022F50SC405 dRight hip BiopsyMultiple thyroid nodulesA few residual pigments in the lesion area and no itching sensation

To identify the allergen, we summarized the reported cases that used patch and intradermal testing to delineate the mechanism of skin hypersensitivity to vitamin K1. Previous studies consistently reported that only the whole preparation of vitamin K1 (in its vehicle) or vitamin K1 alone produced positive test results[19-21]. When the individual components of the vehicles were tested, they almost always yielded negative results. In some cases, patch tests showed negative results, while intradermal tests showed opposite results[23,30], which may, to some degree, reflect insufficient percutaneous absorption. Page et al[37] found that dermatitis from topically applied vitamin K1 was caused by the chemical rather than the base. One study in Australia[32] illustrated the importance of testing with appropriate concentrations of reagents, as patch testing with Konakion Cremophor-EL 2 mg/mL showed a negative result, whereas testing with a 10 mg/mL concentration (the concentration administered at hospitals) showed a strongly positive result. Another study showed relatively high rates of intradermal positivity in control participants (4 of 10 controls)[20]; however, the reactions in controls were not as florid, and in two cases, the reaction was delayed to day 6, which may indicate sensitization.

Previous reports suggested that the underlying cause of the reaction is not phytonadione but rather the vehicle, PEO-CO, which is used as a solubilizer or diluent for several drugs. Although experimental and clinical data are limited, these reactions have been classified as anaphylactoid reactions[38]. Experimental and other evidence suggested that PEO-CO may cause anaphylaxis by releasing histamine, as demonstrated by studies showing its pharmacological action in dogs[39], a memory-mediated reaction involving complement activation[40], and the presence of immunoglobulin G steroid sulfatase antibodies as confirmed by appropriate immunological tests[41]. However, PEO-CO may not be responsible for all anaphylactic events, as demonstrated by two cases of anaphylaxis after the administration of formulations that did not containing PEO-CO[42,43].

Several vitamin K preparations are available that contain different inactive ingredients. Most previous investigators did not use patches or intracutaneous testing for these additional ingredients of vitamin K1. Five investigators tested the components of their particular preparations and obtained negative results[19,21,23,25,30]. These results suggest that the antigen that causes adverse cutaneous reactions is not the inactive ingredient in the mixture but vitamin K itself. Because of the potential for exacerbating the long-lived reactions in our patient, no patch or intracutaneous tests were performed.

Liver disease was previously believed to play a role in the pathogenesis of this allergic reaction[44]; however, six cases of cutaneous reactions to vitamin K1 have been described in patients with no known liver disease[21,24,25]. One study in Japan showed, in 94 documented cases of cutaneous hypersensitivity reactions to vitamin K1, no correlation between vitamin K1 hypersensitivity and liver disease[10]. Nevertheless, as patients with liver disease account for the majority treatment demand for vitamin K1, they may be at an increased risk of developing cutaneous reactions to it. An investigation into the underlying liver dysfunction may be indicated when a patient develops a local eczematous reaction to vitamin K1.

In all reported cases of skin reactions, the dose range was 10-1750 mg[17-36]. One study[20] hypothesized that even a minimum dose can cause an eruption. Some researchers have noted that patients in some of the more recalcitrant cases received the smallest doses[33]. In addition, the dosage of vitamin K seems to have no correlation with the onset of the allergic reaction as confirmed by a study[45] that described sclerodermatous reactions associated with large doses of vitamin K1 100-500 mg. This finding suggests that neither injections nor large doses are required for a sclerodermatous reaction to occur[46]. Our patient had no evidence of preexisting hepatic disease and received a total dose of 40 mg.


Although the incidence of adverse reactions to the subcutaneous injection of vitamin K1 is considerably low, such adverse effects can be devastating. In our case, the patient experienced discomfort only in the area of the local lesions and the disease did not have a particularly serious impact on her daily life. Overall, the disease progressed slowly and was well controlled from onset to follow-up. However, it remains difficult to make an accurate clinical conclusion about this case of hypersensitivity, which creates new challenges and requirements for the diagnosis and treatment of such conditions that, in the future, may be avoided with a more judicious use of this form of vitamin K1 in the clinical setting. In contrast to the previously reported cases, our patient was treated its CM. The key to CM treatment is to accurately identify the syndrome and treat the symptoms. CM may achieve unexpectedly good results in terms of improving the patient’s condition. However, the efficacy, safety, and mechanisms of CM therapy require further investigation. Additionally, whether CM therapy alone or combined with Western medicine has better clinical efficacy for the treatment of these adverse reactions requires confirmation.


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