. 2015 May 21;10(5):e0126971. doi:10.1371/journal.pone.0126971
© 2015 Park et al
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
Table 1. Case studies and case series on adverse events associated with bee venom therapy.
| Study (first author, year) | Country | Number of cases | Reason for BVT | Practitioner type | BVT stimulation feature | Venom typea | Skin test | Injection amount | Concomitant treatment | AE symptoms | AE severityb | AE typec | Mueller classificationd | Diagnosis | Causalitye |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bee sting acupuncture (BSA) and bee venom acupuncture (BVA) | |||||||||||||||
| Alqutub 2011 [2] | Saudi Arabia | 1 case (F/35) | Multiple sclerosis | Local practitioner | BSA | Bees | Not reported | 10 bee stings | Not reported | Fatigue, anorexia, and discoloration of sclera (jaundice) | Severe | Others | - | Hepatotoxicity | Probable |
| An 2001 [16] | Korea | 3 cases a) F/58 | a) Degenerative knee arthritis | a) KMD | a) BVA | Bees | a) Not reported | a) BV injection 2,000:1, 0.35 mL | a) Cold pack | a) Extreme pain, muscular convulsion and tremble, ocular hyperemia, sleepiness, stiffness of limbs, and hyperventilation | a) Severe | a) SR | a) Grade III | a) Pain shock | a) Probable |
| b) F/57 | b) Progressive bulbar paralysis | b) KMD | b) BVA | Bees | b) Not reported | b) BV injection 2,000:1, 0.1 mL | b) Cold pack, acupuncture, pharmacopuncture | b) Extreme pain, facial sweating, asthenia of limbs, pallor face, weak voice, and sleepiness | b) Severe | b) SR | b) Grade III | b) Pain shock | b) Probable | ||
| c) F/54 | c) Amyotropic lateral sclerosis | b) KMD | c) BVA | Bees | c) Not reported | c) BV injection 2,000:1, 0.3 mL | c) Cold pack | c) Extreme pain, facial sweating, asthenia of limbs, pallor face, weak voice, and sleepiness | c) Severe | c) SR | c) Grade III | c) Pain shock | c) Probable | ||
| Bae 2009 [17] | Korea | 1 case (M/76) | Palpable subcutaneous nodule | Not reported | BSA | Bees | Not reported | Not reported | Not reported | Two erythematous plaques, skin ulcerations, and necrosis | Moderate | SP | - | Foreign bodygranuloma | Probable |
| Cheng 2004 [18] | China | 2 cases a) M/2 | a) Repeated respiratory infections | a) MD | a) BSA | Bees | a) Not reported | a) 1 bee sting | a) Not reported | a) Arrhythmia,pallor face, nausea, vomiting, and cold sweats | a) Moderate | a) SR | a) Grade II | a) Anaphylaxis | a) Probable |
| b) M/3 | b) Repeated respiratory infections | b) MD | b) BSA | Bees | b) Not reported | b) 1 bee sting | b) Not reported | b) Arrhythmia,pallor face, nausea, vomiting, and cold sweats | b) Moderate | b) SR | b) Grade II | b) Anaphylaxis | b) Probable | ||
| Cho 2010 [19] | Korea | 1 case (F/37) | Lower back pain | KMD | BVA | Bees | Not reported | Not reported | Not reported | Skin rash, pruritus, arthralgia,fever, and myalgia | Moderate | SR | Grade I | Serum sickness reaction | Probable |
| Herr 1999 [20] | Korea | 1 case (M/64) | Knee arthralgia | Unqualified person | BSA | Bees | Not reported | Not reported | Not reported | Localized edema and pruritus; skin nodules | Moderate | SP | - | Eosinophilic granuloma | Probable |
| Huh 2008 [21] | Korea | 1 case (M/71) | Knee pain | Not reported | BSA | Bees | Not reported | Not reported | Not reported | Dysarthria, dizziness, and left hemiparesis | Severe | SR | Grade III | Pontine and thalamic infarction | Possible |
| Jung 2012 [22] | Korea | 1 case (F/65) | Knee pain | Unqualified person (apitherapist) | BSA | Bees | Not reported | Not reported | Not reported | Nausea, dizziness, weakness, generalized paresthesia, whole-body wheal, diffuse edema, unconsciousness, and death | Severe | SR | Grade IV | Anaphylaxis, disseminated intravascular coagulation (DIC) | Probable |
| Karapata 1961 [23] | Russia | 1 case (M/51) | Hypertensive disorders | Not reported | BVA | Bees | Not reported | Not reported | Not reported | Vomiting, headache, and uremia | Severe | Others | - | Toxic pulmonary edema | Possible |
| Kim 2005 [24] | Korea | 1 case (F/53) | Pain in the scapular region | KMD | BVA | Bees | Not reported | Not reported | Not reported | Localized pruritus and multiple erythematous papules | Moderate | SP | - | Hypersensitivity | Probable |
| Kim 2007 [25] | Korea | 1 case (F/28) | Not reported | Not reported | BVA | Bees | Not reported | Not reported | Not reported | Facial and generalize edema, backache, and abdominal distension | Moderate | SR | Grade II | Minimal change, nephrotic syndrome | Probable |
| Kim 2010 [26] | Korea | 1 case (F/36) | Knee osteoarthritis | KMD | BSA | Bees | Not reported | Not reported | Not reported | Two erythematous plaques and nodules; skin ulcerations | Moderate | SP | - | Foreign body granuloma | Probable |
| Kim 2011 [27] | Korea | 1 case (F/75) | Knee and lower back pain | KMD | SBV and BVA | Bees | Not reported | SBV injection 2.4 mL, BV injection 4,000:1, 1.0 mL | Pharmacopuncture | Facial erythema localized erythema generalized pruritus chest discomfort mild dyspnea | Moderate | SR | Grade II | Anaphylaxis | Probable |
| Kwon 2009 [28] | Korea | 2 cases a) M/76 | a) Lower back pain, knee osteoarthritis | a) KMD | a) SBV | Bees | a) Not reported | a) Not reported | a) Not reported | a) Tongue edema, dysarthria, mild dyspnea, localized erythema, and swelling | a) Severe | a) SR | a) Grade III b) Grade I | a) Anaphylaxis | a) Probable |
| b) F/50 | b) Pain in hand and shoulder joints | b) KMD | b) SBV | Bees | b) Not reported | b) SBV injection 2.2 mL | b) Pharmacopuncture | b) Generalized pruritus and fever | b) Moderate | b) SR | b) Grade I | b) Anaphylaxis | b) Probable | ||
| Lee 1996 [29] | Korea | 1 case (F/43) | Chronic eczema-like dermatosis | Not reported | BSA | Bees | Not reported | Not reported | Not reported | Multiple erythematous plaques and nodules | Moderate | SP | Foreign body granuloma | Probable | |
| Lee 1996 [30] | Korea | 1 case (F/42) | Polyarthralgia | Not reported | BSA | Bees | Not reported | Not reported | Not reported | Localized edema and redness; subcutaneous nodules | Moderate | SP | Foreign body granuloma | Probable | |
| Lee 2000 [31] | Korea | 1 case (M/28) | Ankle sprain | KMD | BVA | Bees | Not reported | Not reported | Not reported | Neck stiffness, chest pressure sensation, stridor, and dyspnea | Severe | SR | Grade III | Anaphylaxis | Probable |
| Lee 2010 [32] | Korea | 1 case (M/59) | Lipoma | Not reported | BSA | Bees | Not reported | Not reported | Not reported | Single erythematous plaques | Moderate | SP | - | Foreign body granuloma | Probable |
| Lee 2011 [33] | Korea | 2 cases a) F/53 | a) Knee and lower back pain | a) MD | a) BVA (apitoxin injection) | Bees | a) Not tested | a) Not reported | a) Not reported | a) Multiple erythematous plaques and nodules, skin ulcerations, and tenderness | a) Moderate | a) SP | a) - | a) Foreign body granuloma | a) Probable |
| b) M/59 | b) Foot pain | b) MD | b) BVA (apitoxin injection) | Bees | b) Not tested | b) Not reported | b) Not reported | b) Multiple erythematous plaques and nodules, skin ulcerations, and tenderness | b) Moderate | b) SP | b) - | b) Foreign body granuloma | b) Probable | ||
| Lee 2013 [34] | Korea | 1 case (M/50) | Back pain | KMD | BSA | Bees | Not reported | Not reported | Not reported | Multiple erythematous plaques and nodules | Moderate | SP | - | Chronic folliculitis and granuloma | Probable |
| Li 2002 [35] | China | 1 case (F/63) | Limb joint pain | MD | BSA | Bees | Not reported | More than 20 bees stings | Not reported | Pallor face, chest discomfort, dyspnea, dysarthria | Severe | SR | Grade III | Anaphylaxis | Probable |
| Li 2005 [36] | China | 4 cases a) F/67 | a) Rheumatoid arthritis | a) Not reported | a) BSA | Bees | a) Not reported | a) 3 bee stings | a) Not reported | a) Generalized pruritus, large amounts of sweat, pallor lip, decreased consciousness, hot feeling of the extremities, chest discomfort, and nausea | a) Severe | a) SR | a) Grade III | a) Anaphylaxis | a) Probable |
| b) F/63 | b) Rheumatoid arthritis | b) Not reported | b) BSA | Bees | b) Not reported | b) Not reported | b) Not reported | b) Pallor pace (blue violet), tachypnea, dysarthria, and dizziness | b) Severe | b) SR | b) Grade III | b) Anaphylaxis | b) Probable | ||
| c) F/59 | c) Rheumatoid arthritis | c) Not reported | c) BSA | Bees | c) Not reported | c) 2 bee stings | c) Not reported | c) Localized edema and redness, and generalized urticaria | c) Moderate | c) SR | c) Grade I | c) Anaphylaxis | c) Probable | ||
| d) F/36 | d) Rheumatoid arthritis | d) Not reported | d) BSA | Bees | d) Not reported | d) 2 bee stings | d) Not reported | d) Systemic papules, generalized pruritus, localized edema, and redness | d) Moderate | d) SR | d) Grade I | d) Anaphylaxis | d) Probable | ||
| Park 1998 [37] | Korea | 1 case (F/52) | Facial papule | Self | BSA | Bees | Not reported | Not reported | Not reported | Ulcerative tumor | Moderate | SP | - | Eosinophilic foreign body granuloma | Probable |
| Park 2000 [38] | Korea | 1 case (M/50) | Not reported | Not reported | BVA | Bees | Not reported | Not reported | Not reported | Severe diaphoresis, dizziness, palpitation, dysarthria, and left hemiparesis | Severe | SR | Grade III | Ischemic stroke | Probable |
| Park 2013 [7] | Korea | 2 cases a) F/44 | a) Arthralgia pain | a) Not reported | a) BSA | Bees | a) Not reported | a) Not reported | a) Not reported | a) Ulcerative tumor | a) Moderate | a) SP | a) - | a) Live bee acupuncture dermatitis | a) Probable |
| b) M/10 | b) Eczema | b) Not reported | b) BSA | Bees | b) Not reported | b) Not reported | b) Not reported | b) Whitish plaques with erythematous papules | b) Moderate | b) SP | b) - | b) Live bee acupuncture dermatitis | b) Probable | ||
| Rhee 2009 [39] | Korea | 1 case (M/49) | A small nodule | Not reported | BVA | Bees | Not reported | Not reported | Not reported | Erythematous tumor | Moderate | SP | - | Giant dermatofibroma | Probable |
| Rho 2009 [40] | Korea | 1 case (F/49) | Knee arthritis | Not reported | BVA | Bees | Not reported | Not reported | Not reported | Fever, dysuria, face edema, and generalized erythematous; popular rash | Moderate | SR | Grade I | Systemic lupus erythematosus | Possible |
| Shim 2011 [41] | Korea | 1 case (M/52) | Paralysis | KMD | BVA | Bees | Not reported | Not reported | Not reported | Multiple erythematous plaques and nodules, skin ulcerations, and tenderness | Severe | SP | - | Mycobacterium chelonae infection | Probable |
| Song 2002 [42] | Korea | 2 cases a) F/42 | a) Pain in the scapular region | a) Unqualified person | a) BSA | Bees | a) Not reported | a) Not reported | a) Not reported | a) Generalized urticaria, facial edema, dyspnea, and chest pain | a) Severe | a) SR | a) Grade II | a) Anaphylaxis | a) Probable |
| b) F/39 | b) Lower back pain | b) Unqualified person | b) BSA | Bees | b) Not reported | b) Not reported | b) Not reported | b) Facial edema, generalized urticaria, pruritus, lower abdomen pain, and dyspnea | b) Severe | b) SR | b) Grade II | b) Anaphylaxis | b) Probable | ||
| Veraldi 1995 [43] | Italy | 1 case (M/65) | Spinal column arthrosis | Not reported | BSA | Bees | Not reported | Not reported | Not reported | Swelling, edema, and numerous inflammatory nodules | Severe | SP | - | Long-lasting subacute inflammatory reaction | Probable |
| Yoo 1994 [44] | Korea | 1 case (M/45) | Lower back pain | Not reported | BSA | Bees | Not reported | Not reported | Not reported | Generalized erythematous plaques | Moderate | SP | - | Contact urticaria | Probable |
| Yoon 2012 [45] | Korea | 2 cases a) M/33 | a) Lower back pain | a) KMD | a) BVA | Bees | a) Tested (negative) | a) BV injection 2,000:1, 0.4 mL | a) Not reported | a) Facial edema, generalized pruritus, erythema, respiratory depression, and fever | a) Severe | a) SR | a) Grade II | a) Hypersensitivity | a) Probable |
| b) F/75 | b) Facial palsy | b) KMD | b) BVA | Bees | b) Tested (negative) | b) BV injection 2,000:1, 0.4 mL | b) Acupuncture, pharmacopuncture, herbal medicine, physical therapy | b) Localized edema | b) Moderate | b) SP | b) - | b) Hypersensitivity | b) Probable | ||
| Youn 2005 [46] | Korea | 2 cases a) F/66 | a) Knee pain | a) KMD | a) BVA | Bees | a) Not reported | a) BV injection 2,000:1, 0.2 mL | a) Acupuncture, pharmacopuncture | a) Chest discomfort, nausea, dizziness, drowsiness, and chills | a) Moderate | a) SR | a) Grade II | a) Anaphylaxis | a) Probable |
| b) M/39 | b) Posterior neck and shoulder pain | b) KMD | b) BVA | Bees | b) Not reported | b) BV injection 2,000:1, 0.3 mL | b) Acupuncture, cupping | b) Chest discomfort, generalized erythema, pruritus, dyspnea, and nausea | b) Moderate | b) SR | b) Grade II | b) Anaphylaxis | b) Probable | ||
| Yu 1998 [47] | Korea | 2 cases a) F/43 | a) Pruritic skin eruption | a) Not reported | a) BSA | Bees | a) Not reported | a) Not reported | a) Not reported | a) Multiple erythematous plaques and nodules, tenderness | a) Moderate | a) SP | a) - | a) Foreign body granulomas | a) Possible |
| b) M/50 | b) Subcutaneous nodule | b) Not reported | b) BSA | Bees | b) Not reported | b) Not reported | b) Not reported | b) Ill-defined subcutaneous nodules | b) Moderate | b) SP | b) - | b) Foreign body granulomas | b) Possible | ||
| Zhang 1994 [48] | China | 2 cases a) M/50 | a) Knee joint soft tissue damage | a) Not reported | a) BSA | Bees | a) Not tested | a) Not reported | a) Not reported | a) Localized edema; two ecphymas | a) Moderate | a) SP | a) - | a) Live bee acupuncture dermatitis | a) Probable |
| b) M/29 | b) Lumbodorsal fibromyalgia | b) Not reported | b) BSA | Bees | b) Not tested | b) Not reported | b) Not reported | b) Generalized pruritus limb paralysis, dyspnea, nausea, vomiting, systemic papules, large amounts of sweat, paralysis, and tremors | b) Severe | b) SR | b) Grade III | b) Anaphylaxis | b) Probable | ||
| Zhong 2005 [49] | China | 1 case (F/51) | Osteoarthritis pain | MD | BSA | Bees | Not reported | 30–40 bee stings | Not reported | Anorexia, listlessness, jaundice | Severe | Others | - | Acute icteric hepatitis | Possible |
| Venom immunotherapy (VIT) | |||||||||||||||
| Anfosso-Capra 1990 [50] | France | 1 case (F/49) | Not reported | Not reported (performed at the hospital) | Rush VIT | Wasps | Tested (positive) | YJV 60 μg | Not reported | Urticaria and cough | Mild | SR | Grade I | Hypersensitivity | Probable |
| Bousquet 1988 [51] | France | 4 cases a) M/42 | a) Treatment of systemic allergic reactions | a) MD | a) VIT | Bees | a) Tested (positive) | a) HBV 50 μg | a) Not reported | a) Angioedema involving the larynx and tracheobronchial tree; hypotension | a) Severe | a) SR | a) Grade III | a) Anaphylaxis | a) Probable |
| b) M/16 | b) Treatment of systemic allergic reactions | b) MD | b) VIT | Bees | b) Tested (positive) | b) HBV 100 μg | b) Not reported | b) Urticaria, tracheobronchial angioedema, and slight hypotension | b) Moderate | b) SR | b) Grade II | b) Anaphylaxis | b) Probable | ||
| c) M/26 | c) Treatment of systemic allergic reactions | c) MD | c) VIT | Bees | c) Tested (positive) | c) HBV 100 μg | c) Not reported | c) Increased pulse rate and decreased blood pressure | c) Severe | c) SR | c) Grade III | c) Anaphylaxis | c) Probable | ||
| d) M/19 | d) Treatment of systemic allergic reactions | d) MD | d) VIT | Bees | d) Tested (positive) | d) HBV 100 μg | d) Not reported | d) Mild hypotension, tachycardia, severe headaches, and erythematous rash | d) Severe | d) SR | d) Grade III | d) Anaphylaxis | d) Probable | ||
| De Bandt 1997 [52] | France | 1 case (M/69) | Desensitization of BV | MD | VIT | Wasps | Tested (positive) | Not reported | Not reported | Motor loss in the left upper limb, weakness of both lower limbs, high grade fever, generalized rash, an indurated erythematous skin lesion over the left forearm, and arthritis of both wrists | Severe | SR | Grade III | Serum sickness reaction | Probable |
| Eming 2004 [53] | Germany | 1 case (F/51) | Desensitization of BV | Not reported | Rush VIT | Bees | Tested (positive) | Not reported | Not reported | Multiple erythematous and subcutaneous nodules | Moderate | SP | - | Panniculitis | Possible |
| Karakurt 2010 [54] | Turkey | 1 case (f/45) | Desensitization of BV | MD | VIT | Bees | Tested (positive) | Not reported | Not reported | Painful cyclic uterine contractions | Moderate | Others | - | Hypocalcemia or electrolyte imbalance | Probable |
| Lyanga 1982 [55] | Canada | 1 case (F/24) | Desensitization of BV | MD | VIT | Wasps | Tested (positive) | Vespid venom 0.433 μg–100 μg | Not reported | Transient bradycardia | Moderate | Others | - | Idiosyncratic or direct toxic effect | Probable |
| Nemat 2011 [56] | Germany | 1 case (F/16) | Desensitization of BV | MD | VIT | Bees | Tested (positive) | Not reported | Not reported | Severe pain affecting the left shoulder, chest wall, and left arm; muscular weakness in left the arm and hand; shortness of breath | Severe | Others | - | Neuralgic amyotrophy | Possible |
| Pijak 2011 [57] | Slovak Republic | 1 case (M/47) | Because of significant professional risk | Not reported | VIT | Wasps | Tested (positive) | Not reported | Not reported | Elevations of aminotransferases and development of nephrotic syndrome | Severe | Others | - | Hepatitis B reactivation complicated with nephrotic syndrome | Probable |
| Reisman 1988 [58] | USA | 7 cases a) F/39 | a) Desensitization of BV | a) MD | a) VIT | Mix | a) Tested (positive) | a) HBV 1.0 μg, YJV 0.1 μg,Polistes venom 0.1 μg | a) Not reported | a) Nausea, emesis, headache, fever, malaise | a) Moderate | a) SR | a) Grade II | a) Late onset reaction | a) Possible |
| b) M/40 | b) Desensitization of BV | b) MD | b) VIT | Mix | b) Tested (positive) | b) HBV 5.0 μg, YJV 2.0 μg | b) Not reported | b) Fatigue, malaise, local swelling | b) Moderate | b) SR | b) Grade I | b) Late onset reaction | b) Possible | ||
| c) M/70 | c) Desensitization of BV | c) MD | c) VIT | Mix | c) Tested (positive) | c) HBV 50.0 μg, YJV 5.0 μg | c) Not reported | c) Generalized aches, joint pain | c) Moderate | c) Others | c) - | c) Late onset reaction | c) Possible | ||
| d) M/37 | d) Desensitization of BV | d) MD | d) VIT | Mix | d) Tested (positive) | d) HBV 0.3 μg, YJV 0.3 μg | d) Not reported | d) Muscle aches, joints sore, difficulty in walking | d) Moderate | d) Others | d) - | d) Late onset reaction | d) Possible | ||
| e) F/41 | e) Desensitization of BV | e) MD | e) VIT | Wasps | e) Not reported | e) YJV 50.0 μg | e) Not reported | e) Chills, fever, aches | e) Moderate | e) SR | e) Grade I | e) Late onset reaction | e) Possible | ||
| f) M/50 | f) Desensitization of BV | f) MD | f) VIT | Wasps | f) Tested (positive) | f) YJV 50.0 μg | f) Not reported | f) Asthma, chest tightness | f) Moderate | f) Others | f) - | f) Late onset reaction | f) Possible | ||
| g) M/27 | g) Desensitization of BV | g) MD | g) VIT | Mix | g) Tested (positive) | g) HBV 0.1 μg, YJV 0.1 μg | g) Not reported | g) Generalized ache, fatigue | g) Moderate | g) SR | g) Grade I | g) Late onset reaction | g) Possible | ||
| Yalcin 2012 [59] | Turkey | 1 case (M/61) | Desensitization of BV | MD | VIT | Bees | Tested (positive) | Not reported | Not reported | Severe itching, erythematous papules, and plaques | Moderate | SP | - | Jessner lymphocytic infiltrate | Possible |
AE: adverse event; BVT: bee venom therapy; BSA: bee sting acupuncture; BVA: bee venom acupuncture; SBV: sweet bee venom; HBV: honeybee venom; KMD: Korean medical doctor; MD: Medical doctor; VIT: venom immunotherapy; YJV: yellow jacket venom.
a Venom type: bees (family Apidae); wasps (family Vespidae); mix (bees and wasps).
b AE severity was assessed using Spilker’s criteria: mild, moderate, and severe.
c AE type was classified into 1 of 3 categories: systemic reaction (SR), skin problem (SP), and other.
d Mueller classification: if a systemic reaction occurred as an AE, it was classified into 1 of 5 categories: large local reaction, grade I, grade II, grade III, and grade IV.
e Causality was determined through the WHO-UMC causality scale: certain, probable, possible, unlikely, conditional, and inaccessible.