EDUCATION AND DEBATE

The toxicology of Latrodectus tredecimguttatus:the Mediterranean Black Widow Spider

MS Bonnet*

Avon Prior, Durley Park, Keynsham, Bristol, BS31 2AT, England, United Kingdom

The symptomatology of envenomation by the Mediterranean Black Widow Spider,Latrodectus tredecimguttatus, is reviewed. The results confirm the hypothesis that thehomeopathic remedy, Tarentula hispanica, is derived from this spider, not from theWolf spider, Lycosa tarentula. Homeopathy (2004) 93, 2733.

Keywords: Black Widow; Latrodectus tredecimguttatus; Lycosa tarentula; Tarentulahispanica; Materia Medica Homeopathie; spiders; toxicology

IntroductionRichardson-Boedler1 has recently proposed that thehomeopathic medicine, Tarentula hispanica, is derivedfrom the Mediterranean Black Widow spider, not fromthe Wolf spider, Lycosa tarentula, as has been assumedhitherto. This article expands on the biology, offering amore complete understanding of the source of thehomeopathic medicine. The section on the venom ismore biochemically and laboratory oriented, while thesymptomatology is presented in a classical repertoryformat. This article has been prompted by the work ofRichardson-Boedler, and my conclusions support herhypothesis.This paper is a compilation of the signs and

symptoms as presented in the literature describing thevictims of envenomation by Latrodectus tredecimgut-tatus. Comparing the Materia Medica of Tarentulahispanica, and also the historical descriptions ofvictims bitten by the tarentula, with the toxicologyof Latrodectus tredecimguttatus suggests that it isresponsible for the hysterical behaviour historicallyassociated with it and its venom that is the source ofthe homeopathic medicine.

The Biology of Latrodectus tredecimguttatus

L. tredecimguttatus belongs to the Order Araneae,Suborder Araneomorphae (Labidognathae), FamilyTheridiidae (the comb-footed spiders),2 which possessvertical chelicerae (fangs) opposing each other, actingin a pincer fashion as the spider holds, pinches andinjects its victim with paralysing toxin while suspendedin the web. This is in contrast to the second suborderOrthognathae (mygalomorph spiders), which dependson gravitational force to produce an effective stabbingaction.3

It has similar morphology to the North Americanblack widow, Latrodectus mactans and the Australianred-back spider, Latrodectus hasselti but is charac-terised by 13 red spots, more or less bright, on itsabdomen4 instead of the red hourglass design on theventer of the former and the red dorsal marking on thelatter (Figure 1).

Synonyms and Nomenclature

Latrodectus mactans tredecimguttatus is the mostcommon synonym.5 Aranea tredecimguttata is an earlysynonym.6,7 The names Latrodectus malmignattus, L.malmignatus7 and L. malmignathus are erroneoussynonyms.8 The genus Latrodectus is erroneouslywritten as Latrodectes, Lathrodectus and Lathro-dectes by various authors.European black widow, Italian black widow, North-

ern Mediterranean black widow, Malmignatta orMalmignatto is the Italian word derived from malus

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*Correspondence: M.S. Bonnet, Avon Prior, Durley Park,Keynsham, Bristol BS31 2AT, England, UK.E-mail: sam.bonnet@gp-l81125.nhs.ukReceived 20 June 2003; revised 4 September 2003; accepted 6October 2003

Homeopathy (2004) 93, 2733r 2003 The Faculty of Homeopathy

doi:10.1016/j.homp.2003.10.001, available online at www.sciencedirect.com

for bad, and mignatta, signifying leech,8 Veuvenoire "a treize points or Malmignatte(France),3,5,9

Viuda negra (Spain),10 Saeuss (Algerian Berber).11

Distribution and habitat

Mediterranean regions,10,12 extending to Saudi Arabiaand all North Africa11 to Ethiopia, Central Asia,Southern Russia and the Caucasus, Southern Eur-ope,9,1316 the Canaries,17 and St Helena.18

L. tredecimguttatus constructs its funnel-shaped webat ground level, in places almost devoid of vegetationconcealing most of it within soil crevices, underneathlarger stones or shrubs, in holes made by otheranimals, in human detritus or piles of wood/stones.6,18,19 The web is haphazard, with no regularoutline for its retreat or for its horizontal funnel. It iscovered with blades of grass with dried bits of plants,wood and animal remains in its wall.18 There is acatching platform; this is very primitive two-dimen-sional, roughly circular, with silk threads radiating likespokes from a central hub.19 The whole complex ispoorly differentiated with its radial arrangement andvertical viscid threads acting as signal threads,19 eventhe connecting corridor consists only of a few threadsof web.18

Only the female is venomous. She measures about 917mm in length.6,17 On the slightest disturbance, shescurries to the deepest part of her web, beyond theseveral egg sacs that she has constructed during herlife-time6 where she curls up with her legs tucked in.She is totally immobile and does not try to attack.11

The male is much smaller (3.25.5mm), has 13 redspots arranged in three longitudinal rows6 and isharmless.Adult males are found fromMay to September while

females live longer, usually until November. Thefemale constructs seven to eight egg sacs from June

to October with 13 weeks in between, each containingabout 450 eggs.6

The eggs are orange-rose in colour and contained ina white globular egg-sac (1417mm 1215mm)with one end pointed. The cocoons are suspended fromthe ceiling deep in the retreat.18 The eggs contain atoxin immunologically indistinguishable from thatfound in the adult spiders venom gland; alpha-latrotoxin.13 The time it takes from oviposition toemergence is about 40 days.6 But, egg sacs that havebeen constructed late in the season, may hibernate toemerge several months later.6 The cocoons areconstantly watched over by the mother.11 The spider-lings, when leaving the cocoon, are black with lightspots which gradually change in colour from brownish-yellow to red.18 At rst, they stay on the web, andscurry back into the safety of the cocoon at theslightest hint of danger.11 Young females require 4months to reach maturity if emerging early spring;otherwise they will take 12 or more months to reachadulthood.6

VenomSpider venoms are complex and contain a variety ofproteins and non-protein components; the majorbiological activities reside in the protein fractions.20

The venom of black widow spiders is a neurotoxin15

that affects the neuromuscular endplates and thesynapses in the central nervous system. The synapticvesicle becomes totally depleted after a massiveexocytotic release of neurotransmitters at central andperipheral synapses. This causes permanent dysfunc-tion of the synapse as one component of the venom,alpha-latrotoxin (alpha-LITx, a vertebrate-specictoxin) binds to cholinergic presynaptic receptors ofvertebrates.3,21 The other polypeptide component,alpha-latroinsectotoxin (alpha-LITx) is active in in-sects but non-toxic for vertebrates.21,22 There are veinsectotoxins in the venom of L. tredecimguttatus inaddition to one crustacean-specic neurotoxin (alpha-LCTx) which affects crabs, craysh, shrimps andwoodlice.2327 The mode of action of the vertebraeand insect toxins are similar28 and on a body weightbasis, have approximately the same toxicity.23

The toxic protein in L. tredecimguttatus has a highmolecular weight, 130,000Da, than that of Atraxrobustus29 (1525,000Da) or Loxosceles reclusa (upto 34,000Da).3033

Spider venoms contain a number of enzymes,depending on the species. Hyaluronidase is present inLatrodectus tredecimguttatus, L. mactans,34 L. ery-thrognatha and in Loxosceles reclusa30,31 venoms.Hyaluronidase increases the diffusion of injectedmaterials injected into the skin, thus facilitating thediffusion of venom.3537 The amino acid gamma-aminobutyric acid is found in the venom of Latrodec-tus tredecimguttatus and that of the Sydney Funnel

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Fig. 1 Latrodectus tredecimguttatus: The MediterraneanBlack Widow Spider.

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Web spider, Atrax robustus,29 but not in the SouthAmerican black widow spider, Latrodectus erythrog-natha. This amino acid modies and blocks the stretch-receptor neuron in crustaceans.35

Spider venoms are also rich in non-protein compo-nents. L. tredecimguttatus venom contains 5-hydroxy-tryptamine (serotonin) at a very low concentration(0.040.08 mg/mg).20,38 Its most important role is toproduce pain, enhancing the defensive action of thevenom.35 At such low concentrations 5HT may mainlyfacilitate the distribution and penetration of the othertoxic components.38 The LD50 of L. tredecimguttatusis 0.331.06 mg/g mouse body weight12 when injectedsub-cutaneously. It is more toxic, at 0.59 mg, intra-peritoneally. The LD50 of Latrodectus mactans ve-nom34 is 1.202.70 mg/g.12,20 Only the brown widowspider of North America, Latrodectus geometricus, ismore lethal than L. tredecimguttatus with a LD50 of0.310.59 mg/g.12

MateriaMedica basedonhumanenvenomation by LatrodectustredecimguttatusOutline

The autonomic nervous system is affected, as indicatedby excessive perspiration, salivation, bronchial, vascu-lar, muscular and sphincter spasm. There is violentpain, centred in the lumbar region, abdomen andthighs due primarily to muscular spasm; an oppressiveheaviness in the chest, hypertension with ECGchanges, polypnea and oliguria. The facies is termedlatrodectismic and includes blepharoconjunctivitis.39

Mind

Agitation,5,40,41 psychomotor:42,43 incidence 1733%10,16

Amnesia/ disturbance of memory.44

Anxiety7,41 and agitation: 26% of cases,5 aboutdeath (child).43

Confusional state, acute16 disorientation in time,person and place44,45 with desperation.46

Aphonia.47

Consciousness normal;41 mental clarity; lucid withanxiety sensation regarding gravity of illness.7

Delirium.11,44,48 with hallucinations,44,45 visual.43

Psychotic state of mind.17

Mental disturbances49 with dyspnea and a precor-dial oppression and anxiety; patient repeatedly puttinghand onto chest.44

Depression and deep sadness with sighing andcrying, even grown men, terried by feelings of theirimpending death.44

Obnubilation 8.33% of cases,10 persistent for dayswith intermittent lucid periods, gradually increasing infrequency.11

Pavor mortis42 and pronounced restlessness.17,39,47

Psychic picture, dramatic.45

Restlessness,6,46,49,50 impulsive, with desire to get upand go away, to leave (more rarely, to jump out ofwindow).44

Rolling in bed, pulling and tearing bedsheet.44

Shouting, yelling, screaming, rolling on oor withhaphazard convulsive movements, uttering incompre-hensible words and terrorised by anybody approach-ing, reacting with desire to stand up, to run away, toescape.44

Speak, incapable of, using gestures to communicate.Torpor, general, profound, with all movements

becoming slow, almost fatigued, with intense asthenia,early symptom.44 Weep, desire to, inexplicable, sud-den, abandoning activity before crying desperatelywithout apparent reason and without answeringquestions, even from close relatives.46

Worry, anxiety, concern; psychomotor: 50% ofcases.10

Central nervous system

Clonic movements.16

Convulsions, worsening on second day,17,40,47,51

with tremors6,42,50 of whole body.52

Fainting;16 coma.48

Meningism:48 negative on rst day; slight, withheadache and vomiting on second.40

Motor incoordination.42

Paraesthesia.16

Paralysis, accid: rarely.42

Psychomotor excitation,45 mornings.11

CSF pressure increased, clear.17,41,47

Abdominal reexes feeble.40

Hyperreexia42 particularly upper limbs.40

Patellar pseudoclonus, bilateral.40

Tendon reexes increased,47 brisk (child),43 constantsymptom.17

Sensation to touch, pinprick, vibration and positionHyperaesthesia.7

Pinprick sensation diminished, local.47

Head pain

Cephalgia: 33% of cases,10,40,42,48 frontal, intense inchild.11,43

Eye

Blepharoconjunctivitis.39,43,49

Conjunctivitis,40,47 with congestion,46 more or lesspronounced in all patients.17

Lachrymation.17,45,49

Miosis48 moderate.11

Mydriasis, some cases.17

Pupils constricted and not reacting to light.50

Changes in the fundus of the eye, some cases,17

marked.47

Fundal veins full.17

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Vision

Accommodation difculties with blurred, hazy vi-sion.16

Nose

Rhinitis.48

Face

Angioedema, facial;48 congested facies,3941 xed(child)43 and swollen,53 with facial hyperhidrosis41

and ushing.46,49

Eyelids oedematous40 and loose tissue below theeyes,47 hyperaemic.17

Facial expression of indescribable terror with facialcongestion and eyelids oedematous with pink edges.44

Pale, anxious.41

Facies Latrodectismica: facial congestion, trismus,rhinitis, blepharoconjunctivitis, mydriasis and cheilitis:6.6% of cases.5,40,43

Hyperaemia of skin in face47 and head, givingcharacteristic appearance.17

Mouth

Salivation,11,49 excessive39,45,47 profuse (up to 1.5 l in24 h) or dry mouth.17

Sialorrhoea: 41.67% of cases.10

Thirst, intense.7,48

Tongue, oedematous.48

Paraesthesia, dental.48

Stomach

Anorexia and constipation.17,45

Heartburn despite normal gastric acidity or evenhypoacidic on gastric juice analysis.17

Dysphagia.40

Nausea and vomiting:5,7,10 1325% of cases,16 afterabout 1 h after start of illness.51

Vomiting, very frequent.17,45,47,51

Abdomen

Abdomen distended, slightly.47

Abdominal contractions: 83.33% of cases,10,40

marked for several hours,14 guarding 50% ofcases;16,49,51 tense, very tender and tympanitic.11

Abdominal musculature rigid47 disappearance ofabdominal reexes.17

Abdominal pains,11 colicky, with abdomen tight andsensitive to touch6,50 and pains radiating to lowerlimbs: 93.3% of cases.5,41

Abdominal pains with contractures in spasms: 66%of cases.43

Liver, pronounced increase in size,17 liver edgepalpable and sensitive to pressure.47 Subicterus:15.38% of cases.17

Abdominal X-ray: normal.41,43,51

Rectum

Diarrhoea.11,48

Urinary system

Dysuria.48

Oliguria39,40,47,49 even with full bladder,17 sometimesdeteriorating to anuria47,49 and retention.45

Albuminuria.7,11,40,47,51

Increased urobilinogen.17

Erythrocytes and leucocytes in urine.7

Glycosuria, rare17(child).43

Granular and cylindrical casts.17

Proteinuria: 25% of cases.10

Male genitalia

Priapism11,45,48,51 with involuntary ejaculation, occa-sionally.44

Chest and respiration

Dyspnea5,7,48 (child):43 13% of cases.16

Tachypnea (25/min 51): 33.33% of cases10,16,47 andsupercial breathing.Heartburn47 and violent precordialgia,5 violent.41

Sensation of heaviness/oppression/pressure in thechest (with fear of death)17,39,40,42,47 and thoracicpains.5,10

Chest X-ray: normal.10,41,43,51

Cardio-vascular system

Tachycardia5,45 33.33% of cases,10 with extrasystoly;7

moderate, early, frequently followed by bradycardia(adrenergic).17,39,45

Blood vessels spasm.39

Arterial hypertension: 41.67% of cases;10,42 usuallytransitory.Hypotension 7%.16

Blood pressure rise to 200/125 (adult);39,40,47,51 150/110 (child).50

Pulse: 72130 beats/min40,41,47,51 small and slow.7

ECG: Abnormalities in 36% of patients.39,41

Bradycardia, sinus: 42/min, P-wave high in lead II &III. QT-interval prolonged: 0.48 s, ST-segment de-pressed.17,39

Tachycardia, sinus in 33%;10 initial and subsequentECGs (day 1). Tall T-waves in leads V2V5 with ST-segment depression in leads V3V5; initial ECG (day1).51 Subsequent ECG (3 h later) shows negative T-waves in leads V1V6 with elevation of ST-segment.51

T-wave very low in lead I; attened in lead II; negativein lead III.39

Echocardiography. Initially: dyskinesia of interven-tricular septum and reduced systolic function. On day5: antero-septal hypokinesia with ejection fraction of0.45.51 On day 8: septum and left ventricular anteriorwall normokinetic with ejection fraction of 0.54.51

Musculo-skeletal system

Local erythematous oedema is followed in a fewminutes by muscular spasms in the trunk and the face,accompanied by violent abdominal pains and neurop-sychic signs.43

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Affected limb, unable to use.40

Arthralgias.48

Hypertonia with muscular contractions.7

Contractions, spastic45 with diffusepains.41

Myalgia, paroxysmal, becoming diffuse and intoler-able,16 particularly abdominal, thoracic and lumbar.42

Rigidity of the musculature, tetany48,49 with tremorsand contractures.45,51

Back

Dorso-lumbar pains/contractions,5,7 violent: 40% ofcases,5,40 may radiate to lower limbs.Upper back pain, along scapular line.5,7

Extremities

Contractures in extremities: 50% of cases.10

Extremities cold and cyanosed.41

Pain in extremities10,40 radiating rst from knee togroin; followed by increased intensity involving abdo-men and chest.47

Paraesthesia of extremities.48

Lymphadenopathy, painful.48

Stiffness of small joints, especially wrists.4

Hyperthermia and paraesthesia (formication) inupper limbs:40 33.350%.5,53

Palmar numbing.4

Heaviness, sudden, throughout legs (rst sensa-tion).46

Marbling of the knees.41

Moving legs, irregular choreiform.46

Pains in lower extremities and plantar burning/stinging sensation.40

Paraesthesia and burning in feet especially in thesoles.5,47,53

Unable to stand upright,40,47 incapable,46 frozen asif had lumbago.17

Walking difculties; tabetic gait, ataxic,40 hypoto-nia.41

Sleep

Insomnia,40 night after night consecutively, withintermittent weeping bouts.46

Insomnia,49 with sensation of being cold all night.44

Fever

Shivers accompanied by profuse sweats: 100% ofcases.43,53

Afebrile (child).43

Fever oscillating between 371C and 37.81C,40 anar-chic: 23% of cases.16

Fever, slight: 33% of cases;5,10 warmth and feelingas if he could burst.47

Perspiration

Hyperhidrosis:7,10,46 2367% of cases,16 local withexcitation of erectores pilorum.17

Sweating, profuse,5,17,42,48,49 cold,51 diffuse.6,50

Skin

The bite site may be erythematous with oedema or aturticoidal, warm and hypoaesthetic,48 or hyperaes-thetic.5,17

Anaesthesia dolorosa.17

Cyanosis.7

Erythema, local: 83% of cases10 with urticaria.17

Erythema, generalised, diffuse (child),43 appearing at2448 h: 17% of cases.16

Necrosis: 20% of cases.16

Oedema, local: 43% of cases,16 soon spreadingregionally.11

Urticaria, generalised/diffuse, erupting on secondday;48 ceased progressively 2 days later.41

Scarlatinoid, morbiliform, papular, or vesicularrash, may be generalised,5 or localised on abdomen,chest or regional, commonly followed by pruritus.17

Maculopapular rash on thorax and abdomen, thirdday.40

Plaques, red, surrounded by urticarial halo, extend-ing rapidly and extensively.41

Purpura involving the trunk and lower limbs: 17%of cases.16

Tumefaction, or slight swelling, reddish, with a tinyhard and blackish tip and intense pruritus.4

Pain

The whole syndrome starts with pain, at rst region-ally, rapidly spreading to resemble an acute abdomen;evolving into spasms, involving the lumbar region andlegs with plantar burning paraesthesia and formica-tion in the upper limbs.48,53 At start of illness, pains inabdomen and lumbar region; on second and thirddays, the pains are greater in lower extremitiesaffecting mostly soles of feet with sharp burningsensations.17

Pain: burning, local, soon radiating to regionallymph nodes with swelling.17

Pain: acute,49 severe, especially in the loins, abdo-men, and extremities.47

Pain: mostly in muscles and bones; as if somebodywas tearing the esh with tongs.17

Pain: constrictive; compressive.7

Pain: lancinating7 initially,53 diminishing graduallyover a few hours, reappearing at later intervals.4

Progressively encompassing whole body.7

Pain: local in10 3767% of cases.16

Pain: loins especially, pressing and cutting.47

Pain: lumbar, violent, exacerbated by pressure onvertebral spines (especially L2L3), radiating intolower limbs.41

Pain: radiating to groin, abdomen, lumbar regionand thorax, becoming paroxysmal.40,48

Haematology

Usually fall in eosinophil and lymphocyte count, witha neutrophil leucocytosis.17

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Haematocrit (Hct): 0.5851 (normal: m0.410.50;f0.350.46).Haemoconcentration47 with a haemoglobin of

19.7 g/dl (normal: m1316 g/dl; f1215 g/dl).40,51

Leucocytosis:47 14,60024,100/ml40,41,49 in 33.33% ofcases10 (normal: 4,00010,800/ml).White blood cell count (WBC): 15,70039,200/mm3

(93% neutrophils) initially, rising to 41,800/mm3 (73%neutrophils)41,51 (normal: 480010,000/mm3).Lymphopenia.47

Biochemistry

Amylase (serum): 254U/l51 (normal: 30170U/l).Aspartate aminotransferase (AST): 100U/l51 (nor-

mal: p42U/l).Lactate dehydrogenase (LDH): 395828U/l41,51

(normal: p270U/l).Blood urea nitrogen (BUN): 72mg/dl47 (normal: 7

30mg/dl).Cardiac enzymes initially normal.51

Creatinine phosphokinase (CPK): 590999 IU/l(adult);5,41,51 child: 201 IU/l41,43 (normal o200 IU/l).Calcaemia: 2.75mmol/l41 (normal: 2.122.57mmol/

l).Hyperglycaemia49 or hypoglycaemia, slight, in some

cases.17

Hyperglycaemia: 11.4mmol/l (with glycosuria)43

(normal: 3.34.4mmol/l).Hypoazotaemia: 8.0mmol/l43 (normal: 1421mmol/

l).Liver metabolism, disordered, temporarily.47

General

Asthenia, prolonged: 13%16 and marked.7

Convalescence prolonged, one month or more,17

with intermittent psycho-motor agitation crisies, gra-dually improving.46

Debilitation and loss of appetite even a month afterillness.40

Weakness, extreme.6,50

Weight loss is characteristic, up to 5 kg in 3 days.17

Autopsy

Brain: perivascular haemorrhages (experimental mam-mals).54

Liver: hepatic cells swollen (30min to 6 h) increasinggradually to dissociation of cells, massive hyperaemia,and pericapillary oedema (10+h); necrobiosis (12 h)and lobular necrosis (24 h)(experimental mammals).54

Adrenals, enlargement.47

Zona fasciculata cells swollen, vacuolated or nelygranular, followed (in 24 h) by disorganisation of thecolumns (experimental mammals).54

Spleen and lymph nodes: hyperaemia (early), fol-lowed by lymphoid depletion, lymphorrhexis andhaemosiderosis (experimental mammals).54

Thymus: thymic cells show marked pyknosis andkaryorrhexis (12 h); reticulum cells swollen and pro-minent (experimental mammals).54

Renal: Capillary thrombosis (40 h) (experimentalrats).54

Renal: Cortex enlargement.47

Kidneys: degeneration of tubular epithelium (1020 h) with necrosis (24 h) (experimental mammals).54

Zona fasciculata, Zona glomerulosa and Zona reticu-laris enlarged.47

Lungs: pale and inated (mice).12

Lungs: reddish marbled appearance with numerouspetechiae (mice).12

Pulmonary oedema (experimental mammals).54

Heart: perivascular haemorrhages (experimentalmammals).54

Differential diagnosis

Acute abdomen.10

Appendicitis.41

Acute myocardial infarction.10,41

Delirium tremens.10

Dissection of aorta.10,41

Peritonitis.41

Renal colic.41

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ARTICLE IN PRESS

Latrodectus tredecimguttatusMS Bonnet

33

Homeopathy

The toxicology of Latrodectus tredecimguttatus: the Mediterranean Black Widow SpiderIntroductionThe Biology of Latrodectus tredecimguttatusSynonyms and NomenclatureDistribution and habitat

VenomMateria Medica based on human envenomation by Latrodectus tredecimguttatusOutlineOutlineMindCentral nervous systemHead painEyeVisionNoseFaceMouthStomachAbdomenRectumUrinary systemMale genitaliaChest and respirationCardio-vascular systemMusculo-skeletal systemBackExtremitiesSleepFeverPerspirationSkinPainHaematologyBiochemistryGeneralAutopsyDifferential diagnosis

References