Temperature: A Critical Factor Determining Localization and Natural History of Infectious, Metabolic, and Immunological Diseases

TEMPERATURE: A CRITICAL FACTOR DETERMINING LOCALIZATION AND NATURAL HISTORY OF INFECTIOUS, METABOLIC, AND IMMUNOLOGICAL DISEASES DAVID RODBARD,* HELENA WACHSLICHT-RODBARD, ï AND SIMON RODBARDt Enormous attention has been given to the characteristic fevers which occur in the course of infectious diseases [1, pp. 46, 52, 70; 2]. Relatively little attention has been given to the effects ofregional body temperature differentials on disease processes [3]. The human body is not a uniform incubator at 370C. Instead, there are significant temperature gradients from trunk to extremities [4, pp. 102-105; 5], from hand to fingertips [6], within the external ear [7], anterior chamber of the eye [8], or wherever two veins happen to cross [9] (figs. 1-4). This temperature profile depends on geographic location, climate, season, humidity, activity , clothing, levels of thyroid hormones, glucocorticoid and sex steroids, and time of day [10, pp. 160, 161]. In many tropical regions, the skin temperature gradients are relatively constant year-round, possibly contributing to susceptibility to several chronic infections which might be eradicated or supposed by the wider temperature swings in the temperate zones [10, 11]. We shall briefly review some of the evidence in support of the hypothesis : Body temperature is a critical factor determining host susceptibility, We are grateful to Drs. Frank Neva, Hyman Zimmerman, Griff T. Ross, C. C. Shepard, and F. Hawking, who provided critical reviews of the manuscript; and to Drs. Gildo del Negro and Carlos da Silva Lacaz ofthe Institute ofTropical Medicine, University of Säo Paulo, for their stimulating discussions and an opportunity to examine patients with paracoccidioidomycosis, sporotrichosis, and leishmaniasis. ?Biophysical Endocrinology Section, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20205. tWashington Hospital Center, Washington, D.C. 20010. ^Deceased May 1, 1975. Formerly Department of Cardiology, City of Hope Medical Center, Duarte, California 91010.© 1980 by The University of Chicago. 0031-5982/80/2303-0176$01.00 Perspectives in Biology andMedicine · Spring1980 | 439 4Of Heart, Kidney Tympanic Membrane I 35 Forehead Chest Thigh 30l· Rectum Liver, Brain Testis-Varicocoele Back Nostril Arm Forearm 40fM| Liver, Abdominal Cavity, Rectal Mouth Lumbar Muscles, Infra-Abdominal Testis Lungs, Lymph Nodes, Abdominal WaN Brain, Skin of Abdomen, Parietal Bone Base of Ear, Frontal Bone Lower Eyelid 35 HiJ Outer Surface of Ear, Nasal E Cornea, Eyes Open Paw Pad¦ Scrotum {Surface of Testis) 30 Leg Eartobe 25 Finger-Dorsum 25 Laboratory (Ambient) 20> Temperature CC)® 20} Temperature CC) Fig. !.—Temperature profiles. A, Man [7, 10]; B, Rabbit [45, 73] Fig. 2.—Thermogram, male and female, whole body, anterior and posterior views. Reproduced with permission from [4]. 440 Fig. 3.—Thermogram, man, hand. Reproduced with permission from [6] Fig. 4.—Thermogram, man, ear. Reproduced with permission from [7] 441 location of lesions, and the natural history of disease. This principle has been previously enunciated for individual diseases—for example, pneumonia [12], other bacterial and mycobacterial diseases [13-17], fungal diseases [18], viral diseases [19, pp. 532, 598, 706; 20, pp. 74, 131, 144, 158, 231, 325, 350; 21], and protozoal diseases [22-26]. However, the enormous generality of this principle in clinical medicine (table 1) has not been fully appreciated or exploited [3]. This thesis has numerous corollaries with regard to pathogenesis, diagnosis, treatment, and epidemiology of infectious, metabolic, immunological, and neoplastic diseases. TABLE 1 Lesions of Cool Sites Lesions of Warm Sites Syphilis Gonorrhea Chancroid Diphtheria Bacterial endocarditis Septicemias Pneumonitis, meningitis Pyelonephritis, cystitis Typhoid fever, enteric fevers Mycobacterial Leprosy "Swimming pool" granuloma (Bovine tuberculosis) (Avian tuberculosis) Fungal Superficial dermatophytoses Candidiasis Sporotrichosis Paracoccidioidomycosis Lobos's disease Cryptococcal meningitis Coccidioidomycosis Rocky Mountain spotted fever Rickettsialpox Typhus: epidemic, endemic, scrub Q fever Viral Variola Influenza Common cold Plantar warts Hand, foot, and mouth disease Varicella Poliomyelitis Equine encephalitis Cytomegalic inclusion disease Encephalmyocarditis Protozoal Mucocutaneous Leishmaniasis Cutaneous Leishmaniasis Kala azar Amoebiasis Toxoplasmosis Falciparum malaria 442 D. Rodbard, H. Wachslicht-Rodbard, and S. Rodbard ¦ Temperature and Disease TABLE 1 (Continued) Lesions of Cool SitesLesions of Warm Sites Microfilaria! (Edesonfilaria malayensis)*Loa loab (Monnigofilaria setariosa)a GoutNormal bone formation PseudogoutCalcification of basal ganglia Ectopic calcificationsOligospermia 2° varicocoele Hyperlipidemia: xanthomas Cystinosis Immunological Cryoglobulinemia Henoch-Schönlein purpura Cold urticaria Paroxysmal cold hemoglobinuria Cold agglutinins Angioneurotic edema...