1185

with genuine immersion-foot problems and wet-sock abrasions. The terminology in published reports was no less confusing.3-5,7-10 We shall confine ourselves to the terms tropical immersion foot (T.i.F.) (fig. 1), a condition in which the ankles and dorsa of the feet become red, swollen, and tender after protracted exposure to water at tropical temperatures (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

Occasional

Survey

TROPICAL IMMERSION FOOT

ALFRED M. ALLEN
Division of Preventive Medicine, Walter Reed Army Institute of Research, Washington, D.C. 20012, U.S.A.

DAVID TAPLIN

Departments of Dermatology and Epidemiology and Public Health, University of Miami School of Medicine, Florida 33152, U.S.A.

syndrome Tropical-immersion-foot studied in U.S. Army units in Vietnam. The principal characteristics were: temporary inability to walk due to painful swollen feet; history of protracted exposure (>72 hours) to relatively warm water (22-32°C); erythema, œdema, and tenderness of the skin covering the ankles and dorsa of the feet; chronic inflammation and vasculitis of the upper dermis, with maceration of the stratum corneum; and pronounced variation in individual susceptibility to immersion injury. Complete healing occurred promptly after drying and elevation of the feet. Tropical immersion foot (T.I.F.) is a different disease from warm-water immersion foot (W.W.I.F.), which is a syndrome characterised by painful, white,
Summary
was

Classic immersion foot has been recognised for at least a century and a half. It is a form of non-freezing cold injury. Thousands of cases occurred among U.S. military forces in Europe during the 1939-45 war, and at times the frequency was high enough to seriously jeopardise military operations.l1 Many of the afflicted men had loss of tissue and permanent disability as a result of this kind of injury. The In contrast, T.i.F. is a relatively new disease. original description was based on cases among American soldiers fighting to retake the Philippines during the 193945 war.8 Glenn 10 examined a hundred and twenty of the men within 12 hours of admission to evacuation hospitals and noted that the signs and symptoms closely resembled those of immersion injuries sustained in cold climates. Consequently this new syndrome was believed to be a type of cold injury low on the gradient".8 War"

wrinkled soles. Evidence suggests that T.I.F. is caused by an effect of water itself on the dermis, whereas W.W.I.F. is due to hyperhydration of the plantar
stratum corneum.
INTRODUCTION

LATELY, immersion injuries of the feet have attracted attention because of the large number of foot casualties among U.S. combat forces in Vietnam.1.2 A transient condition of painful, white, wrinkled soles has been well described by various terms which include

tropical-immersion-foot (T.i.F.) syndrome,3,4 warmwater immersion foot (w.w.r.F.),5.6 and paddy-field

foot/
We describe a more severe condition, which also occurred in Vietnam, with signs and symptoms similar to minimal cold injury, and attempt to resolve the 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 and often disabling diseases of the skin were occurring in epidemic proportions. Methods included clinical examination of cases, review of hospital records and official reports, and biopsy of lesions. Samples were taken while accompanying infantrymen on patrol in inundated terrain.
DEFINITION AND TERMINOLOGY

Before the introduction of medical-research teams into Vietnam, there was considerable difficulty in interpreting reports from field commanders and medical personnel who described foot casualties, often in alarming numbers, as " immersion foot ", " paddy foot ", tropical-jungle foot ", and " jungle rot ". Foot and lower-leg infections due to dermatophytosis and pyoderma were intermixed
"

Note oedema and and ankle.

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

1186
Because of the tactical situation, the men were unable their wet boots and socks at night, and were often required to march, stand, and sleep in water to waist level and above for periods ranging from 4 to 10 days. The first indication of injury was a burning sensation in the feet, more pronounced on the dorsal surfaces than on the soles. Walking became progressively more painful, prompting the men to remove their footwear in order to examine their feet. Many of those who did so soon found that their feet had become so swollen that they could not replace their boots. They were in obvious distress whenever they attempted to walk and were no longer fit for combat duty. Severe cases often had to be evacuated by air to 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 there was tenderness to deep pressure over the involved surfaces. Pain and tenderness were increased by weight-bearing. The skin was cool on admission, but became warm within 12 hours. Pulses were full and capillary filling was brisk. Wet-sock abrasions and small ulcerations over pressure-points were commonly found in association with T.I.F. Hyperhydration and wrinkling of the plantar surfaces was an early but transient feature. In contrast to the original descriptions of T.I.F., systemic reactions were present in nearly every case severe enough to require admission to hospital. The reactions consisted of fever and femoral lymphadenopathy. Oral temperatures ranged between 38 and 39°C. Femoral lymph-nodes were moderately enlarged and 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 medications were used. Systemic antibiotics were given only if the patient had a concomitant infection for which an antibiotic was indicated. Recovery generally required no more than 4 or 5 days in hospital. Even the most severely affected patients healed completely within 10 to 12 days. In contrast with cold immersion injuries, gangrene did not 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 pain and tenderness, and reversal of the changes involving the soles. This occurred within the first 48 to 72 hours after admission. After this time, the erythema of the dorsal surfaces and ankles was replaced by diffuse ecchymotic blotches, crops of tiny vesicles, and a fine maculopapular rash. (Edema subsided over 4-7 days. After there had been a fine, branny of the skin over the involved areas, desquamation the skin of the feet appeared completely normal, and there were no detectable vasomotor changes. Although there were no permanent physical
to remove

Fig. 2-W.W.I.F.

Injury

is confined to the soles.

time restrictions precluded confirmatory studies. No photographs or biopsies were obtained. Fungal cultures were negative, leading Hopkins and Webster to suggest that the essential pathogenic factor was maceration of the stratum comeum due to prolonged immersion.12 In late 1965, U.S. Marines in the northern coastal provinces of South Vietnam began sustaining massive wet-foot casualties after long patrols in water-soaked fields and paddies.6,11 Anderson5 noted that the principal findings were confined to the soles of the feet, which were white, wrinkled, and painful, especially during weight-bearing. Most patients recovered completely in 1 to 3 days on conservative therapy alone. Anderson termed this form of injury warm-water-immersion
"

foot ". In 1966, the painful, white wrinkled-sole syndrome was produced in five of six volunteers after 36 to 72 hours of immersion in Florida swamp water (temperature 1S-21°C). Topical applications of silicone grease were effective in prevention.3 These findings were confirmed by Buckels et al.5 working with Marines in North Carolina. In 1967, paired foot studies showed that experimentally produced immersion foot was not due to cold injury, but in fact occurred more rapidly at higher water temperatures.4 Painful, wrinkled soles were avoided by allowing the 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 superficial fungal and bacterial infections, immersion injuries of the feet often accounted for more time lost from combat duty than all other medical causes combined. These conditions were often the chief limiting factor in the duration of combat operations.
CLINICAL

CHARACTERISTICS

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

changes, interviews with patients, physicians, and military commanders indicated than men who had had a severe attack of T.I.F. were more susceptible to a second or third episode.

1187
more

severely affected cases there was oedema and extravasation of erythrocytes into the upper dermis. The oedematous areas were located primarily around the blood-vessels and in the dermal papillae; in these areas the colloidal-iron stain revealed the presence of acid mucopolysaccharides. But perhaps the most important finding was a definite and in some cases pronounced narrowing of the dermal capillaries due to swelling and proliferation of the endothelial lining. The epidermis showed moderate acanthosis and parakeratosis with swelling and fragmentation of the superficial layers of the stratum corneum. In six cases there were hyphas within the epidermis, often within keratin and parakeratin at the margins of an intraepidermal abscess. The hyphae were minute and delicate; parts appeared to be regenerated or granular. The appearance of the organism was consistent with that of Dermatophilus congolensis. There was no evidence of intravascular thrombosis or fat necrosis suggestive of frank cold injury.
EPIDEMIOLOGY

Fig. 3-Section of skin from the dorsum of the foot showing typical histopathological changes of T.LF. Note chronic inflammatory-cell dermatitis and perivasculitis

( x 35).
_____________

Many cases of T.I.F. without oedema and systemic reactions were treated in forward areas. These cases were characterised by pain, tenderness, and erythema and resolved completely within 2 or 3 days if the feet
were one of several afflictions of the skin of the feet that were common after prolonged exposure to the watery delta environment. Accurate differential diagnosis was therefore of critical importance as a guide to proper treatment. In contrast to was cellulitis T.I.F., streptococcal usually unilateral, with intensely painful swelling of the leg. Dermatophytosis was distributed in patches and confluent rings rather than in the diffuse yet symmetrical fashioncharacteristic of T.I.F. Wet-sock erosions were confined to areas of friction and pressure, such as the area under the bootlaces, and did not extend over the entire surface of the dorsum and ankle, as did the lesions of T.I.F.

T.I.F. was

kept dry. only

The occurrence of T.I.F. was strictly limited to men who had spent 3 or more consecutive days in inundated terrain, yet injury developed in only a fraction of those at risk, despite apparently equal exposures. Commanders estimated that severe immersion injury developed in only three or four of each hundred men exposed to a wet environment over a 4-day period, and this impression was confirmed during interviews with patients. T.i.F. occurred throughout the year in the Mekong Delta, but was most common during the rainy season. There were striking seasonal differences in rainfall, but practically none in ambient temperature, relative humidity, and the temperature of surface waters. During the dry season cases of T.I.F. were confined to units in tidal river basins or heavily irrigated terrain. T.i.F. was not as common as dermatophytosis and pyoderma.2 Not a single case was detected in four hundred and ninety-six infantrymen, nearly a third of whom had significant bacterial or fungal infections of 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 only predictive indicator was that of previous immersion

injury.
COMMENT

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

HISTOPATHOLOGY

principal variant,

W.W.I.F.

(see accompanying table).

taken from the dorsa of Biopsy specimens the feet of twelve men with T.I.F. of varying degrees of severity. Ten of the men were White, two were Black, and two had experienced previous episodes of T.I.F. while in Vietnam. Despite the differences in race, severity of lesions, and past history of injury, the histological findings were remarkably similar in every case. The principal finding was a chronic dermatitis and vasculitis involving the upper dermis (fig. 3). The inflammatory-cell infiltrate consisted primarily of small lymphocytes with a sprinkling of monocytes, eosinophils, and, more rarely, plasma-cells. In the
were

Two different forms of injury can occur after exposures to water which appear similar in every respect except duration. The reason for this difference is not as yet known; however, observations regarding duration of exposure are consistent with existing knowledge of the biological properties of thick and thin stratum In vitro the stratum corneum acts as a corneum. medium into which water permeates diffusion passive at a relatively constant rate, but the thick stratum corneum on the palms and soles is far more permeable than the thin stratum corneum covering the rest of the body, including the ankles and dorsa of the feet. IS Thick stratum corneum becomes fully saturated with-

1188 in 3 days of continuous exposure to water, whereas the water barrier in thin stratum corneum remains intact for up to 3 days after exposure, and only after this time is water allowed to pass. This may explain the differences between the length of exposure required to produce injury of the dorsum of the foot as compared to the sole. Warm-climate immersion injuries are obviously related to prolonged exposure of the feet to water, but their exact aetiology remains unknown. Clinical studies have suggested several theories, including exposure of the feet to water coupled with dehydration and malnutrition,14 maceration and hyperhydration of the stratum corneum,12 and cold injury." However, none of these ideas has been confirmed. W.W.I.F. was exactly reproduced under controlled environmental conditions, and individuals with heavy, calloused soles were at highest risk 3°5 Biopsy specimens have revealed only hyperhydration of the plantar stratum corneum,15 suggesting that the condition is primarily due to the mechanical effects of " waterlogging " of the weight-bearing surfaces. The soles
DISTINGUISHING FEATURES OF T.I.F. AND W.W.I.F.

Feature

T.I.F.

W.W.I.F.

Clinical: Site of involvement

Ankles and dorsa of feet

Soles

Symptoms

Burning pain aggravated by pressure

from footwear and

Pain
"

on weightbearing ; tingling; walking on rope

"

Signs

by walking Symmetrical erythema, cedema and tenderness; line of

demarcation at boottop -level Fever and femoral

sensation

Swelling, wrinkling, and pallor

Systemic involvement

None

Healing

time

lymphadenopathy (severe cases) 3-10 days

1-3

days

Pathology: Epidermis
Dermis

Parakeratosis and Thickening of acanthosis stratum corneum Chronic inflammator5 y No observed changes cells (lymphocytes, monocytes, eosinophils, and plasmacells) in upper

dermis; angiitis
with endothelial

proliferation; diapedesis; cedema

Pathogenesis (presumptive)

Passage of water through compromised epidermal

barrier into upper dermis; reaction to hypotonic fluid

Hyperhydration (" water-logging ") of plantar stratum

corneum

- Epidemiology:

Water exposure

required
Water temperature

3-7

days

1-3

days

producing injury
Relation to water temperature

22-32OC (70-90°F) Not established

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

Susceptibility factors

Previous episodes of T.r.F. increase

Thickness of plantar
stratum corneum:

susceptibility
Prevention

heavy callouses predispose; thin

soles protect

become convoluted and rigid, accounting for the pain walking, which was best described by one of our volunteers as like having waffle irons in the boots. True T.I.F. syndrome has yet to be produced experimentally, but lesions with gross and microscopic features reminiscent of T.I.F. have been induced in volunteers. In a majority of nineteen marine subjects an erythematous, papular rash developed on the dorsum of the foot and lower leg after continuous immersion in water-filled boots for 7 days Biopsy of the papules revealed a lymphocytic vasculitis of the upper and mid dermis, with diapedesis of red bloodcells. Willis 16 induced similar changes on the legs and backs of thirty volunteers after 72-144 hours of continuous exposure of the skin to water held in place by small plastic cups. In these experiments the temperature of the water was approximately equal to that of the surrounding unoccluded skin, and the intensity of the inflammation could not be related to the pH or the bacterial flora of the water samples. This suggested that water itself, having entered the dermis through water-damaged stratum corneum, may be responsible for the dermatitis. In neither of the experimental studies IS,16 was there mention of the presence of filamentous organisms in the epidermis similar to those found in half of our biopsied cases in Vietnam. The importance of these organisms is difficult to assess, and they might be involved in the aetiology of naturally occurring immersion injury. T.I.F. can be prevented by limiting the duration of The threshold of exposure exposure to water. for is not well defined, but casualrequired injury ties in Vietnam could be virtually avoided by insisting " on 24-hour dry out " periods between each 48-hour of period exposure to wet terrain. At times such were measures impractical or unfeasible, and therefore 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; and although preliminary data suggested that the use of these 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 immersion injury of the dorsum was equally common in both silicone-treated and untreated feet i5 The damaging effects of prolonged water immersion on the skin are increasingly recognised in civilians. Immersion injuries can disable any susceptible individual who is exposed to suitable environmental conditions.6 Housewives, bartenders, farmers, and certain industrial workers are at considerable risk.16 Hyperhydrated skin is more susceptible to agents which might otherwise be tolerated-e.g., housewives eczema, paronychia in dishwashers, and hand dermatitis in milling-machine operators. The recognition, management, and prevention of immersion injuries deserves continued study.
on

Day-long drying of
feet between 2-3day periods of
constant wetness

Overnight drying of feet; daily application of silicone

grease

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

1189 Requests for reprints should be addressed

to

A. M.

A.,

Division of Preventive Medicine, Walter Reed Army Institute of Research, Washington, D.C. 20012, U.S.A.
REFERENCES
1. Sulzberger, 2. Allen, A. M.,

operated
pressure

M. B.,

Akers, W. A. Archs Derm. 1969, 100, 702.

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-

Taplin, D., Lowy, J. A., Twigg,

leave air in the chamber during the cycle, so that bottles in the lowest layer did not reach sterilising temperature. Because bottles for bacteriological control were taken from the top layer of the load a chance of detecting this failure was lost, and the batch was issued for use although some of the bottles contained viable bacteria, most of which were of gram-negative species.!
was to

7. 8.

delphia, 1971. Lancet, 1967, i, 1043. 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. 11. 12. 13. 14. 15.

16.

Glenn, F. in Activities of Surgical Consultants in World War II (edited by B. N. Carter); vol. 1, p. 492. Washington, 1962. J. Am. med. Ass. 1967, 200, 716. Grauer, F. H. in Preventive Medicine in World War II (edited by E. C. Hoff); vol. 5, p. 105. Washington, 1960. Scheuplein, R. J., Blank, I. H. Physiol. Rev. 1971, 51, 702. White, J. C. New Engl. J. Med. 1943, 228, 241. Douglas, J. S., Eby, C. S. Milit. Med. 1972, 137, 386. Willis, I. J. invest. Derm. 1973, 60, 166.

Public Health
INTRAVENOUS INFUSION OF CONTAMINATED DEXTROSE SOLUTION
The

Devonport Incident
M. W. CALDER

P. D. MEERS
Public Health

Laboratory, Greenbank Devon

Hospital, Plymouth,

G. M. LAWRIE* M. M. MAZHAR Plymouth General Hospital, Plymouth, Devon

The manufacture, faulty sterilisation, Summary distribution, and use of part of a batch of 5% dextrose intravenous solution is described. Some of the bottles were bacterially contaminated, and the contents of some of these were infused into patients. Certain details of the patients affected, at least four of whom died of acute endotoxic shock, are recorded. The multiplication of three of the organisms isolated from the bottles was followed experimentally in dextrose solution, and the resulting endotoxin levels were estimated. At room temperature in this fluid gram-negative species of bacteria reached counts of about 107 organisms per ml. in 3 weeks, falling slowly to 104-105 per ml. after 11 months. These findings accorded well with counts found in contaminated bottles of the same age.
HISTORY
OF

THE

INCIDENT

A BATCH of some 4000 500 ml. bottles of 5 % dextrose intravenous injection was heat-sterilised at a factory near Liverpool on April 6, 1971, in several autoclaves. One of these machines, in which about 600 bottles were processed in three layers, was faulty. It has been deduced that the effect of the fault together with the way the autoclave was
* Present address: Prince Henry Hospital, Sydney, Australia.

Though the batch-number printed on the label of each bottle bore a suffix identifying the autoclave in which it had been processed, this information was not recorded, so the complete distribution of the sub-batch which had been in the faulty machine is unknown. It is certain, however, that a delivery of 720 bottles of 5% dextrose made to a wholesaler in Devon in May, 1971, included at least a proportion of the sub-batch, and that some or all of them remained in the wholesalers warehouse until early 1972, when they were sent to the Devonport Section of the Plymouth General Hospital. In the interval between their autoclaving and this point, the bacteria present in the unsterilised bottles had grown into large populations and it was in this condition that they began to reach wards and departments at the end of February and the beginning of March, 1972.1 Patients infused with the contents of the average contaminated bottle of this sub-batch of 5 % dextrose solution suffered profound acute endotoxic shock. In many of the cases this was so rapidly fatal as to obscure the cause of death, but when a number of individuals were similarly affected over a period of 4 days, and when this included two otherwise fit patients who had had elective surgery, an investigation took place which led to the discovery of the contaminated bottles. The incident attracted national 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 cause had 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 evidence connecting most of them with identifiable bottles of fluid. However, a convincing causal relationship between the infusion of a bottle of 5% dextrose solution and the onset of otherwise inexplicable circulatory collapse was demonstrated in five patients, four of whom died. Some details of these patients are given in table i. There were two others who died in circumstances suggesting, but with less certainty, that they, too, had been infused with contaminated fluid. All these patients were having intravenous infusions of 5% dextrose solution when their collapsed state was noticed. In most cases the infusions were not stopped, and one patient was given a second probably contaminated bottle of the fluid. It is notable that the three severely affected patients who survived more than an hour or so developed pulmonary oedema. Postmortem 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 organism resembling one of those found in the contaminated bottles were isolated. 2 partly used bottles of 5% dextrose of the incriminated batch were examined bacteriologically ; both were contaminated. Part of the contents
case

of 1 of these had almost

certainly been given

case

to

4, and the infusion of the other into

5, the

last of the series, was stopped before the patient reached the stage of irreversible shock. At the time this was happening a meeting of surgical staff was concluding that 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 intravenous fluids postoperatively. After this meeting elective surgery