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Occasional Survey

TROPICAL IMMERSION FOOT

ALFRED M. ALLEN

Division of Preventive Medicine, Walter Reed ArmyInstitute of Research, Washington, D.C. 20012, U.S.A.

DAVID TAPLIN

Departments of Dermatology and Epidemiology andPublic Health, University of Miami School of Medicine,

Florida 33152, U.S.A.

Summary Tropical-immersion-foot syndromewas studied in U.S. Army units in

Vietnam. The principal characteristics were: tem-

porary inability to walk due to painful swollen feet;history of protracted exposure (>72 hours) to rela-tively warm water (22-32°C); erythema, œdema, andtenderness of the skin covering the ankles and dorsaof the feet; chronic inflammation and vasculitis ofthe upper dermis, with maceration of the stratum

corneum; and pronounced variation in individual sus-ceptibility to immersion injury. Complete healingoccurred promptly after drying and elevation of thefeet. Tropical immersion foot (T.I.F.) is a differentdisease from warm-water immersion foot (W.W.I.F.),which is a syndrome characterised by painful, white,wrinkled soles. Evidence suggests that T.I.F. is caused

by an effect of water itself on the dermis, whereasW.W.I.F. is due to hyperhydration of the plantarstratum corneum.

INTRODUCTION

LATELY, immersion injuries of the feet have attractedattention because of the large number of foot casual-ties among U.S. combat forces in Vietnam.1.2 A tran-sient condition of painful, white, wrinkled soles hasbeen well described by various terms which includetropical-immersion-foot (T.i.F.) syndrome,3,4 warm-

water immersion foot (w.w.r.F.),5.6 and paddy-fieldfoot/We describe a more severe condition, which also

occurred in Vietnam, with signs and symptoms simi-lar to minimal cold injury, and attempt to resolvethe existing confusion in terminology.The information in our report was collected during

a study of cutaneous diseases carried out between

October, 1968, and March, 1969, when severe andoften disabling diseases of the skin were occurringin epidemic proportions. Methods included clinicalexamination of cases, review of hospital records andofficial reports, and biopsy of lesions. Samples weretaken while accompanying infantrymen on patrol ininundated terrain.

DEFINITION AND TERMINOLOGY

Before the introduction of medical-research teams intoVietnam, there was considerable difficulty in interpretingreports from field commanders and medical personnel whodescribed foot casualties, often in alarming numbers, as

" immersion foot ", " paddy foot ", "

tropical-junglefoot ", and " jungle rot ". Foot and lower-leg infectionsdue to dermatophytosis and pyoderma were intermixed

with genuine immersion-foot problems and wet-sockabrasions. The terminology in published reports was noless confusing.3-5,7-10We shall confine ourselves to the terms tropical immer-

sion foot (T.i.F.) (fig. 1), a condition in which theankles and dorsa of the feet become red, swollen, andtender after protracted exposure to water at tropicaltemperatures (22-32°C), and warm-water immersion foot(w.w.i.F.) (fig. 2), to describe white, painful, wrinkled,waterlogged soles.

BACKGROUND AND MILITARY IMPORTANCE

Classic immersion foot has been recognised for at leasta century and a half.’ It is a form of non-freezing coldinjury. Thousands of cases occurred among U.S. militaryforces in Europe during the 1939-45 war, and at timesthe frequency was high enough to seriously jeopardisemilitary operations.l1 Many of the afflicted men had lossof tissue and permanent disability as a result of this kindof injury.

In contrast, T.i.F. is a relatively new disease. The

original description was based on cases among Americansoldiers fighting to retake the Philippines during the 1939-45 war.8 Glenn 10 examined a hundred and twenty ofthe men within 12 hours of admission to evacuation hos-

pitals and noted that the signs and symptoms closelyresembled those of immersion injuries sustained in coldclimates. Consequently this new syndrome was believedto be " a type of cold injury low on the gradient".8 War-

Fig. 1-T.LF. 4 days after hospital admission.Note oedema and desquamation of epidermis from the dorsum

and ankle.

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Fig. 2-W.W.I.F. Injury is confined to the soles.

time restrictions precluded confirmatory studies. Nophotographs or biopsies were obtained. Fungal cultureswere negative, leading Hopkins and Webster to suggestthat the essential pathogenic factor was maceration of thestratum comeum due to prolonged immersion.12

In late 1965, U.S. Marines in the northern coastalprovinces of South Vietnam began sustaining massivewet-foot casualties after long patrols in water-soakedfields and paddies.6,11 Anderson 5 noted that the principalfindings were confined to the soles of the feet, whichwere white, wrinkled, and painful, especially duringweight-bearing. Most patients recovered completely in1 to 3 days on conservative therapy alone. Andersontermed this form of injury " warm-water-immersionfoot ".

In 1966, the painful, white wrinkled-sole syndromewas produced in five of six volunteers after 36 to 72 hoursof immersion in Florida swamp water (temperature1S-21°C). Topical applications of silicone grease wereeffective in prevention.3 These findings were confirmed byBuckels et al.5 working with Marines in North Carolina.

In 1967, paired foot studies showed that experimentallyproduced immersion foot was not due to cold injury, butin fact occurred more rapidly at higher water tempera-tures.4 Painful, wrinkled soles were avoided by allowingthe feet to dry overnight before re-immersion.4,5

There were many cases of immersion injury in U.S.

Army ground combat units operating in wet, lowland

areas, such as the Mekong Delta.1,2 Together with super-ficial fungal and bacterial infections, immersion injuriesof the feet often accounted for more time lost fromcombat duty than all other medical causes combined.These conditions were often the chief limiting factor inthe duration of combat operations.

CLINICAL CHARACTERISTICS

The clinical features of T.I.F. in the MekongDelta of Vietnam were similar to those described inthe south-west Pacific during the 1939-45 war.8,IO

Because of the tactical situation, the men were unableto remove their wet boots and socks at night, andwere often required to march, stand, and sleep inwater to waist level and above for periods rangingfrom 4 to 10 days.The first indication of injury was a burning sensa-

tion in the feet, more pronounced on the dorsal sur-faces than on the soles. Walking became progressivelymore painful, prompting the men to remove theirfootwear in order to examine their feet. Many ofthose who did so soon found that their feet hadbecome so swollen that they could not replace theirboots. They were in obvious distress whenever theyattempted to walk and were no longer fit for combatduty. Severe cases often had to be evacuated by airto hospitals in the rear.On admission there was pronounced pitting oedema

of the ankles and dorsa of the feet, intense erythema,and a clear line of demarcation at boot-top level.The skin was unusually sensitive to touch and therewas tenderness to deep pressure over the involvedsurfaces. Pain and tenderness were increased byweight-bearing. The skin was cool on admission,but became warm within 12 hours. Pulses were fulland capillary filling was brisk. Wet-sock abrasionsand small ulcerations over pressure-points were com-monly found in association with T.I.F. Hyperhydra-tion and wrinkling of the plantar surfaces was an earlybut transient feature.

In contrast to the original descriptions of T.I.F.,systemic reactions were present in nearly every casesevere enough to require admission to hospital. Thereactions consisted of fever and femoral lymphadeno-pathy. Oral temperatures ranged between 38 and39°C. Femoral lymph-nodes were moderately enlargedand tender, but there was no lymphangitis.Treatment consisted of bed-rest, elevation of the

feet, and medication to relieve pain and induce sleep.The feet were left uncovered and no topical medica-tions were used. Systemic antibiotics were givenonly if the patient had a concomitant infection forwhich an antibiotic was indicated.

Recovery generally required no more than 4 or 5days in hospital. Even the most severely affectedpatients healed completely within 10 to 12 days. Incontrast with cold immersion injuries, gangrene didnot occur and we know of no serious sequelx. All

patients were able to return to duty after treatment.The first indications of improvement were loss of

fever and adenopathy, pronounced reduction in painand tenderness, and reversal of the changes involvingthe soles. This occurred within the first 48 to 72hours after admission. After this time, the erythemaof the dorsal surfaces and ankles was replaced bydiffuse ecchymotic blotches, crops of tiny vesicles,and a fine maculopapular rash. (Edema subsidedover 4-7 days. After there had been a fine, brannydesquamation of the skin over the involved areas,the skin of the feet appeared completely normal, andthere were no detectable vasomotor changes.

Although there were no permanent physicalchanges, interviews with patients, physicians, andmilitary commanders indicated than men who hadhad a severe attack of T.I.F. were more susceptible toa second or third episode.

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Fig. 3-Section of skin from the dorsum of the foot showingtypical histopathological changes of T.LF.

Note chronic inflammatory-cell dermatitis and perivasculitis( x 35).

_____________

Many cases of T.I.F. without oedema and systemicreactions were treated in forward areas. These caseswere characterised by pain, tenderness, and erythemaand resolved completely within 2 or 3 days if the feetwere kept dry.

T.I.F. was only one of several afflictions of the skinof the feet that were common after prolonged expo-sure to the watery delta environment. Accuratedifferential diagnosis was therefore of critical impor-tance as a guide to proper treatment. In contrast to

T.I.F., streptococcal cellulitis was usually unilateral,with intensely painful swelling of the leg. Dermato-

phytosis was distributed in patches and confluent

rings rather than in the diffuse yet symmetrical fashion-characteristic of T.I.F. Wet-sock erosions were con-fined to areas of friction and pressure, such as the areaunder the bootlaces, and did not extend over the entiresurface of the dorsum and ankle, as did the lesionsof T.I.F.

HISTOPATHOLOGY

Biopsy specimens were taken from the dorsa ofthe feet of twelve men with T.I.F. of varying degreesof severity. Ten of the men were White, two wereBlack, and two had experienced previous episodesof T.I.F. while in Vietnam. Despite the differencesin race, severity of lesions, and past history of injury,the histological findings were remarkably similar inevery case.The principal finding was a chronic dermatitis and

vasculitis involving the upper dermis (fig. 3). The

inflammatory-cell infiltrate consisted primarily ofsmall lymphocytes with a sprinkling of monocytes,eosinophils, and, more rarely, plasma-cells. In the

more severely affected cases there was oedema andextravasation of erythrocytes into the upper dermis.The oedematous areas were located primarily aroundthe blood-vessels and in the dermal papillae; in theseareas the colloidal-iron stain revealed the presenceof acid mucopolysaccharides. But perhaps the mostimportant finding was a definite and in some casespronounced narrowing of the dermal capillaries dueto swelling and proliferation of the endothelial lining.The epidermis showed moderate acanthosis and

parakeratosis with swelling and fragmentation of thesuperficial layers of the stratum corneum.

In six cases there were hyphas within the epidermis,often within keratin and parakeratin at the marginsof an intraepidermal abscess. The hyphae were

minute and delicate; parts appeared to be regeneratedor granular. The appearance of the organism wasconsistent with that of Dermatophilus congolensis.There was no evidence of intravascular thrombosis

, or fat necrosis suggestive of frank cold injury.

EPIDEMIOLOGY

The occurrence of T.I.F. was strictly limited to menwho had spent 3 or more consecutive days in inun-dated terrain, yet injury developed in only a fractionof those at risk, despite apparently equal exposures.Commanders estimated that severe immersion injurydeveloped in only three or four of each hundred menexposed to a wet environment over a 4-day period,and this impression was confirmed during interviewswith patients.

T.i.F. occurred throughout the year in the MekongDelta, but was most common during the rainy season.There were striking seasonal differences in rainfall,but practically none in ambient temperature, relativehumidity, and the temperature of surface waters.

During the dry season cases of T.I.F. were confinedto units in tidal river basins or heavily irrigated terrain.

T.i.F. was not as common as dermatophytosis andpyoderma.2 Not a single case was detected in fourhundred and ninety-six infantrymen, nearly a thirdof whom had significant bacterial or fungal infectionsof the skin of the ankles and dorsa of the feet.There was little to indicate why some men were

especially susceptible to immersion injury. The onlypredictive indicator was that of previous immersioninjury.

COMMENT

The description provided in our paper permits aclear distinction to be made between T.i.F. and its

principal variant, W.W.I.F. (see accompanying table).Two different forms of injury can occur after exposuresto water which appear similar in every respect exceptduration. The reason for this difference is not as yetknown; however, observations regarding duration ofexposure are consistent with existing knowledge ofthe biological properties of thick and thin stratumcorneum. In vitro the stratum corneum acts as a

passive diffusion medium into which water permeatesat a relatively constant rate, but the thick stratumcorneum on the palms and soles is far more permeablethan the thin stratum corneum covering the rest ofthe body, including the ankles and dorsa of the feet. ISThick stratum corneum becomes fully saturated with-

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in 3 days of continuous exposure to water, whereasthe water barrier in thin stratum corneum remainsintact for up to 3 days after exposure, and only afterthis time is water allowed to pass. This may explainthe differences between the length of exposure re-

quired to produce injury of the dorsum of the foot ascompared to the sole.Warm-climate immersion injuries are obviously

related to prolonged exposure of the feet to water, buttheir exact aetiology remains unknown. Clinicalstudies have suggested several theories, includingexposure of the feet to water coupled with dehydra-tion and malnutrition,14 maceration and hyperhydra-tion of the stratum corneum,12 and cold injury.’"However, none of these ideas has been confirmed.

W.W.I.F. was exactly reproduced under controlledenvironmental conditions, and individuals with heavy,calloused soles were at highest risk 3°5 Biopsy speci-mens have revealed only hyperhydration of the plantarstratum corneum,15 suggesting that the condition is

primarily due to the mechanical effects of " water-

logging " of the weight-bearing surfaces. The soles

DISTINGUISHING FEATURES OF T.I.F. AND W.W.I.F.

Feature

Clinical:Site of involvement

Symptoms

Signs

Systemic involve-ment

Healing time

Pathology:Epidermis

Dermis

Pathogenesis (pre-sumptive)

Epidemiology: -’Water exposure

requiredWater temperature

producing injuryRelation to water

temperature

Susceptibility factors

Prevention

T.I.F.

Ankles and dorsa offeet

Burning pain aggra-vated by pressurefrom footwear andby walkingSymmetrical ery-thema, cedema andtenderness; line ofdemarcation at boot-top -levelFever and femorallymphadenopathy(severe cases)

3-10 days

Parakeratosis andacanthosis

Chronic inflammator5cells (lymphocytes,monocytes, eosino-phils, and plasma-cells) in upperdermis; angiitiswith endothelialproliferation;diapedesis; cedema

Passage of waterthrough compro-mised epidermalbarrier into upperdermis; reaction tohypotonic fluid

3-7 days

22-32OC (70-90°F)Not established

Previous episodes ofT.r.F. increasesusceptibility

Day-long drying offeet between 2-3-day periods ofconstant wetness

W.W.I.F.

Soles

Pain on weight-bearing ; tingling;" walking on rope "

sensationSwelling, wrinkling,and pallor

None

1-3 days

Thickening ofstratum corneum

y No observed changes

Hyperhydration(" water-logging ")of plantar stratumcorneum

1-3 days

15-32°C (60-90°F)Increase in tempera-ture hastens injury

Thickness of plantarstratum corneum:

heavy callousespredispose; thinsoles protect

Overnight drying offeet; daily appli-cation of siliconegrease

become convoluted and rigid, accounting for the painon walking, which was best described by one of ourvolunteers as like having waffle irons in the boots.True T.I.F. syndrome has yet to be produced experi-

mentally, but lesions with gross and microscopicfeatures reminiscent of T.I.F. have been induced involunteers. In a majority of nineteen marine sub-

jects an erythematous, papular rash developed on thedorsum of the foot and lower leg after continuousimmersion in water-filled boots for 7 days Biopsyof the papules revealed a lymphocytic vasculitis of theupper and mid dermis, with diapedesis of red blood-cells. Willis 16 induced similar changes on the legsand backs of thirty volunteers after 72-144 hours ofcontinuous exposure of the skin to water held in placeby small plastic cups. In these experiments the

temperature of the water was approximately equal tothat of the surrounding unoccluded skin, and the

intensity of the inflammation could not be related tothe pH or the bacterial flora of the water samples.This suggested that water itself, having entered thedermis through water-damaged stratum corneum, maybe responsible for the dermatitis.

In neither of the experimental studies IS,16 was theremention of the presence of filamentous organisms inthe epidermis similar to those found in half of ourbiopsied cases in Vietnam. The importance of theseorganisms is difficult to assess, and they might beinvolved in the aetiology of naturally occurring immer-sion injury.

T.I.F. can be prevented by limiting the duration ofexposure to water. The threshold of exposurerequired for injury is not well defined, but casual-ties in Vietnam could be virtually avoided by insistingon 24-hour " dry out " periods between each 48-hourperiod of exposure to wet terrain. At times suchmeasures were impractical or unfeasible, and there-fore alternative means of prevention were explored.Lightweight, fast-drying items of footwear were

developed as possible alternatives to the standard

jungle boot and cotton-wool sock combination; andalthough preliminary data suggested that the use ofthese items would retard the onset of immersion

injury, wet-terrain operations were stopped before

large-scale studies could be initiated.Silicone grease was effective in the prevention of

W.W.I.F. 3,S; however, in an experimental study immer-sion injury of the dorsum was equally common inboth silicone-treated and untreated feet i5The damaging effects of prolonged water immer-

sion on the skin are increasingly recognised in civi-lians. Immersion injuries can disable any susceptibleindividual who is exposed to suitable environmentalconditions.6 Housewives, bartenders, farmers, andcertain industrial workers are at considerable risk.16Hyperhydrated skin is more susceptible to agentswhich might otherwise be tolerated-e.g., housewives’eczema, paronychia in dishwashers, and hand derma-titis in milling-machine operators. The recognition,management, and prevention of immersion injuriesdeserves continued study.

We thank Dr Elson B. Helwig for reviewing the pathologicalmaterial and Mr Robert E. Weaver and Mr Ray A. Drewry fortechnical assistance. This study was supported in part by theU.S. Army Medical Research and Development Command.

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Requests for reprints should be addressed to A. M. A.,Division of Preventive Medicine, Walter Reed Army Instituteof Research, Washington, D.C. 20012, U.S.A.

REFERENCES

1. Sulzberger, M. B., Akers, W. A. Archs Derm. 1969, 100, 702.2. Allen, A. M., Taplin, D., Lowy, J. A., Twigg, L. Milit. Med. 1972,

137, 295.3. Taplin, D., Zaias, N. ibid. 1966, 131, 814.4. Taplin, D., Zaias, N., Blank, H. J. Am. med. Ass. 1967, 202, 546.5. Buckels, L. J., Gill, K. A., Jr., Anderson, G. T. ibid. 1967, 200, 681.6. Anderson, G. T. in Cutaneous Lesions of the Lower Extremities

(edited by M. H. Samits and A. S. Dana, Jr.); p. 168. Phila-delphia, 1971.

7. Lancet, 1967, i, 1043.8. Whayne, T. F., DeBakey, M. E. Cold Injury, Ground Type, in

World War II; p. 211. Washington, 1958.9. Pillsbury, D. M., Livingood, C. S. in Internal Medicine in World

War II (edited by W. P. Havens, Jr.); vol. 3, p. 600. Washington,1968.

10. Glenn, F. in Activities of Surgical Consultants in World War II(edited by B. N. Carter); vol. 1, p. 492. Washington, 1962.

11. J. Am. med. Ass. 1967, 200, 716.12. Grauer, F. H. in Preventive Medicine in World War II (edited by

E. C. Hoff); vol. 5, p. 105. Washington, 1960.13. Scheuplein, R. J., Blank, I. H. Physiol. Rev. 1971, 51, 702.14. White, J. C. New Engl. J. Med. 1943, 228, 241.15. Douglas, J. S., Eby, C. S. Milit. Med. 1972, 137, 386.16. Willis, I. J. invest. Derm. 1973, 60, 166.

Public Health

INTRAVENOUS INFUSION OF

CONTAMINATED DEXTROSE SOLUTION

The Devonport Incident

P. D. MEERS M. W. CALDER

Public Health Laboratory, Greenbank Hospital, Plymouth,Devon

M. M. MAZHAR G. M. LAWRIE*

Plymouth General Hospital, Plymouth, Devon

Summary The manufacture, faulty sterilisation,distribution, and use of part of a

batch of 5% dextrose intravenous solution is de-scribed. Some of the bottles were bacterially con-taminated, and the contents of some of these wereinfused into patients. Certain details of the patientsaffected, at least four of whom died of acute endotoxicshock, are recorded. The multiplication of threeof the organisms isolated from the bottles was

followed experimentally in dextrose solution, and theresulting endotoxin levels were estimated. At room

temperature in this fluid gram-negative species ofbacteria reached counts of about 107 organisms perml. in 3 weeks, falling slowly to 104-105 per ml. after11 months. These findings accorded well with countsfound in contaminated bottles of the same age.

* Present address: Prince Henry Hospital, Sydney, Australia.

HISTORY OF THE INCIDENT

A BATCH of some 4000 500 ml. bottles of 5 %dextrose intravenous injection was heat-sterilisedat a factory near Liverpool on April 6, 1971, inseveral autoclaves. One of these machines, in whichabout 600 bottles were processed in three layers,was faulty. It has been deduced that the effect ofthe fault together with the way the autoclave was

operated was to leave air in the chamber during thepressure cycle, so that bottles in the lowest layerdid not reach sterilising temperature. Because bottlesfor bacteriological control were taken from the toplayer of the load a chance of detecting this failurewas lost, and the batch was issued for use althoughsome of the bottles contained viable bacteria, mostof which were of gram-negative species.!Though the batch-number printed on the label of each

bottle bore a suffix identifying the autoclave in whichit had been processed, this information was not recorded,so the complete distribution of the sub-batch which hadbeen in the faulty machine is unknown. It is certain,however, that a delivery of 720 bottles of 5% dextrosemade to a wholesaler in Devon in May, 1971, includedat least a proportion of the sub-batch, and that some orall of them remained in the wholesaler’s warehouse untilearly 1972, when they were sent to the Devonport Sec-tion of the Plymouth General Hospital. In the intervalbetween their autoclaving and this point, the bacteria

present in the unsterilised bottles had grown into largepopulations and it was in this condition that they beganto reach wards and departments at the end of Februaryand the beginning of March, 1972.1

Patients infused with the contents of the average con-taminated bottle of this sub-batch of 5 % dextrose solutionsuffered profound acute endotoxic shock. In many of thecases this was so rapidly fatal as to obscure the causeof death, but when a number of individuals were similarlyaffected over a period of 4 days, and when this includedtwo otherwise fit patients who had had elective surgery,an investigation took place which led to the discoveryof the contaminated bottles. The incident attractednational publicity, and a Committee of Inquiry was set

up which took evidence and published a report}By the time the contamination was discovered, all

but one of the patients who were to die from this causehad already done so, and although it was known which

type of intravenous fluid they had been given, in what

quantity, and when, there was no longer any evidenceconnecting most of them with identifiable bottles offluid. However, a convincing causal relationship betweenthe infusion of a bottle of 5% dextrose solution and theonset of otherwise inexplicable circulatory collapse wasdemonstrated in five patients, four of whom died. Somedetails of these patients are given in table i. There weretwo others who died in circumstances suggesting, butwith less certainty, that they, too, had been infusedwith contaminated fluid. All these patients were havingintravenous infusions of 5% dextrose solution when theircollapsed state was noticed. In most cases the infusionswere not stopped, and one patient was given a second

probably contaminated bottle of the fluid. It is notablethat the three severely affected patients who survived morethan an hour or so developed pulmonary oedema. Post-mortem examinations were made in two of the four

patients listed in table i who died shortly after collapsing;from the lungs of both large numbers of an organismresembling one of those found in the contaminatedbottles were isolated. 2 partly used bottles of 5%dextrose of the incriminated batch were examined bac-teriologically ; both were contaminated. Part of the con-tents of 1 of these had almost certainly been given to

case 4, and the infusion of the other into case 5, thelast of the series, was stopped before the patient reachedthe stage of irreversible shock. At the time this was

happening a meeting of surgical staff was concludingthat there must be a common cause for the series of

deaths, because all the patients had shown signs of

gram-negative endotoxic shock and had had intravenousfluids postoperatively. After this meeting elective surgery