Fatal Heat Stroke: A Case Report and Literature Review

Abstract

As known in forensics, heat stroke deaths diagnosis is made by exclusion. In fact, in heat-related deaths, the gross and histologic postmortem findings are not pathognomonic, and biochemical investigations are not specific. Therefore, in such cases, a detailed examination of the circumstantial data and autopsied findings is necessary to exclude other possible causes of death. A case of fatal heat stroke of an elderly woman is reported. This case was diagnosed by examining the above elements in combination with immunohistochemical detection of heat shock proteins (HSPs). We then performed a narrative review of the literature on the subject to compare our case with similar ones. In view of the diagnostic complexity of heat-related deaths, we consider it essential to outline the state of the art on this topic. Our results may be a useful tool to orient forensic investigations into these types of deaths.

1. Introduction

Heat stroke (HS) is a condition of sudden and significant increase in body temperature. It may be due to exposure to high environmental temperature (“non-exertional HS”) and/or to intense physical exercise (“exertional HS”) [1]. In both cases, if the body fails to dissipate the heat, it can trigger multi-organ damage that can be irreversible and at times lethal.

Due to climate change, the risk of heat stroke death is increasing in all regions of the world. As recently highlighted by the World Health Organization, scientific evidence has shown that between 2000 and 2019 there were approximately 489,000 heat-related deaths each year, of which 45% were in Asia and 36% were in Europe [2]. In the summer of 2022, there was a record number of deaths from heat stroke, and Italy ranked first among European countries, with more than 18,000 deaths. [3]. In addition, despite increased awareness and prevention on the issue, child heat stroke deaths in vehicles remain frequent. According to a report published by the National Safety Council, in 2023 there were 29 cases in the United States [4].

The “National Association of Medical Examiners Ad Hoc Committee on the Definition of Heat-Related Fatalities” suggests the use of two different terms to indicate fatal heat strokes. It is preferable to use the term “heat stroke death” or “hyperthermia death” only for cases where an antemortem body temperature is ascertained to be ≥40.6 °C (≥105 °F). Instead, the Association recommends the use of the definition “heat-related death” in cases where the antemortem body temperature is unknown, but circumstantial data suggest prolonged exposure of the decedent to high ambient temperature, and another independent cause of death cannot be identified [5]. Although the extension of the definition was crucial to reducing the risk of underestimating deaths (body temperature at collapse can rarely be established and therefore cannot be considered as the sole diagnostic element), the risk of underestimation remains substantial. In fact, the ambient temperature is also often not detected or is not indicative; moreover, in these types of deaths, there are no macroscopic or microscopic findings with pathognomonic value, and they are variable depending on the type and duration of exposure to heat. Postmortem biochemical investigations—e.g., myoglobin or pituitary hormones levels—have also been shown to be nonspecific [6] and only useful as a diagnostic confirmation in the presence of other suggestive elements [7]. Consequently, the diagnosis of heat-related death results from a combination of circumstantial antemortem data, investigative and forensic observations, and nonspecific autopsy findings. Although heat deaths remain diagnoses of exclusion, postmortem immunohistochemical detection of heat shock proteins (HSPs) can be a useful support. HSPs are intracellular chaperones of variable molecular weight induced by stress conditions [8]. HSPs can be induced in response to various physiological and pathological conditions, such as hyperthermia, infection, cancer, ischemic stimuli, hypertension, and atherosclerosis, as well as exposure to toxic substances [9,10,11,12,13,14,15]. Because HSPs are not specific heat-related death markers, their use in forensics is discussed. They are most often used as vitality markers for exposure to high temperatures. In other words, the immunohistochemical representation of HSP expression could be useful in differentiating between vital and postmortem heat exposure [16].

2. Case Report

We report the case of a 75-year-old woman who was found dead in August at around 19:00 p.m. in the outskirts of Rome. At the place of discovery, the vegetation was abundant and varied but not high enough to create shaded areas. According to local weather reports, the outside temperature on that day was 30 degrees, with peaks of 35 degrees and a humidity rate > 60%.

According to the testimony of her children, the woman lived alone about 2 miles away from the place of discovery. Presumably, that morning, the woman had left the house after having breakfast. This hypothesis was based on the finding of food residues on the dining table that were absent the night before. The day before, one of the children had gone to his mother’s house to assist her. The next morning, the children tried unsuccessfully to contact their mother, so they alerted the police.

Based on medical records of the attending physician, the woman was in perfect physical health. However, she had been diagnosed with dementia (of unspecified origin) two years earlier. The woman was assisted by her children at a distance and often by a neighbor who was away on summer holidays. Based on the testimonies collected, the woman needed assistance because in recent months she had experienced serious memory gaps and spatial and temporal disorientation.

The subject was found supine and wearing only a cotton tank top and cotton underpants. No personal objects were found next to the body. They were all found at the house.

Rigor mortis was widespread in all muscles. The hypostases were pinkish, fixed, and located on the back side of the body. The body temperature was not measured.

The external examination of the corpse showed skin slippage and erythema in the areas exposed to direct sunlight and not covered by clothes. These signs were compatible with superficial sunburn. Only early signs of decomposition were found such as clouding of the cornea and greenish discoloration of the skin of the anterior abdominal wall.

The examination of the body was negative for defensive and offensive injuries.

A complete autopsy was performed.

The body was 155 cm long and weighed about 40 kg (Body Mass Index of about 16.6 kg/m²).

The brain was edematous and congested. The lungs were edematous and congested, and petechial hemorrhages were detected over pleural surfaces. The heart walls were free of lesions. Serial sectioning of the coronary arteries showed widespread calcifications and no critical stenosis (≤50%).

The gastric mucosa, the spleen, and the renal surface bilaterally showed petechial hemorrhages. The stomach and the bladder were empty. The gross examination of other organs was unremarkable.

A routine microscopic histopathological study was performed by using formalin-fixed paraffin-embedded tissue sectioned at 4 µm and stained with hematoxylin–eosin and Weigert elastic.

In addition, immunohistochemical investigations of the scalp, brain, left arm skin, and right arm skin samples were performed utilizing monoclonal antibodies anti-heat shock protein (HSP 27, 70, 90).

Samples of skeletal muscle were taken from the biceps brachii and pectoralis major muscles. A histological examination of striated muscles showed only marked edema in the absence of necrosis and structural alterations.

The liver was also widely congested, and only disseminated erythrocytes were found in the perifollicular area of the spleen.

The kidneys showed signs of acute tubular necrosis and neutrophil infiltration.

The microscopic structure of the lungs was characterized by acute emphysema with rupture of the alveolar septa. Red blood cells and macrophages were present.

The toxicology test, performed on a blood sample, was negative for drugs, alcohol, and the most common psychotropic drugs.

The cutaneous heat injury was confirmed by the positive results to the immunohistochemical reaction for HSP 27, 70, and 90 (Figure 1). Instead, the immunohistochemical reaction of the brain was only positive for HSP 70 and 90 (Figure 2).

The cause of death was attributed to acute cardiorespiratory failure caused by heat stroke.

3. Discussion

To compare our case with similar ones and to outline the state of the art on heat stroke deaths, we performed a narrative review on the topic. Between November 2023 and January 2024, we searched case reports of heat stroke deaths in scientific databases (PubMed, Google Scholar, Web of Science) using the terms “death by heat stroke”, “death by heat”, and “fatal heat stroke”. We carried out a first selection of articles by reading the titles and abstracts; this selection was carried out individually by two authors. Then, two other authors performed the second selection by studying the articles and identifying the final study sample.

We report and summarize the salient results of a literary review of cases of fatal heat stroke in

Table 1. Summarized literature review on heat stroke deaths.

	Age	Circumstantial Data	Body T (°C)	External Exam	Autopsy Findings	Histological Findings	Other Results
Wegner A et al. (2021) [16]	77-year-old man	Discovered death in a sauna. The man was a recovered alcoholic.	-	The body was partially mummified.	Considerably limited because of the putrefaction.	Fatty degeneration of the myocardium and coronary sclerosis. Irregular enlargement of the myocytes and areas of myocardial fibrosis.	No expression of HSPs 27, 60, or 70 in the kidneys or lungs. Intense aquaporin 3 expression in the epidermis.
	73-year-old woman	Discovered death in a sauna. The woman had only been in the sauna for about 35 min. She had arterial hypertension and Parkinson’s disease	-	Extensive detachments of the epidermis with map-like desiccations and an incipient penetration of the venous network.	Calcification of the aortic valve and low-grade aortic sclerosis and cholecystolithiasis.	Adipose infiltration of the myocardium, especially in the wall of the left ventricle. Thickening of the intima of the coronary arteries.	Expression of heat shock proteins 27, 60, and 70 in the lung and kidney tissue.
Goodyear JE et al. (1979) [17]	4-month-old male infant	Heat hyperpyrexia death during sleep due to overwrapped too many layers of clothes and blankets in a very warm room.	--	Unremarkable.	Petechiae on the visceral pleura, pericardium, and thymus gland.	Unremarkable.	--
Chao TC et al. (1981) [18]	Ten men with ages ranging from 18 to 29 years old.	Heat stroke collapses during or after physical exercise. Time interval from collapse to heat stroke death varied from 45 min to 99 h 5 min.	At time of admission to the hospital, the rectal temperature ranged from 40 °C to 42 °C.	Cutaneous ecchymoses in two cases.	Diffuse pulmonary hemorrhages. Blood-stained fluid in the trachea and bronchi. Congestion and edema of the brain with petechial hemorrhages into the white matter. Diffuse mucosal hemorrhages in the stomach, duodenum, and small intestines in 7 cases. Hemorrhages in the myocardium, into the renal pelvis, and, in 2 cases, in the adrenal glands. Congestion and fatty change in the liver.	Findings mostly consistent with diffuse hemorrhagic diathesis. Multi-visceral hemorrhages most present in the lung and gastrointestinal tract. Multi-visceral thrombi and congestion. Renal tubular necrosis in all cases. Pituitary infarct in 1 case.	Immunofluorescence microscopy studies in 2 cases: fibrin clots in the capillaries and arterioles of much of the viscera.
Parnell CJ et al. (1986) [19]	17-year-old boy, territorial army basic trainee.	Heat stroke collapse during a 6 km march/run and carrying around 12 kgs of equipment. He died few hours after admission to hospital.	On admission to hospital, rectal temperature was 40 °C.	Unremarkable.	Unremarkable.	Unremarkable except for acute renal tubular damage signs.	--
R. Sherman, et al. (1989) [20]	29-year-old man	Occupational death due to heat stroke. He died on admission to hospital.	Body temperature of 38 °C.	Unremarkable.	Pulmonary congestion, edema, and diffuse fatty change of the liver.	--	Traces of ethanol in the vitreous humor.
	29-year-old man	Occupational collapse due to heat stroke. He died 33 days after admission to hospital.	On admission to the hospital, the axillary temperature was 39 °C.	Unremarkable.	Related to multisystem failure. (Bilateral organizing hemothorax, hemoperitoneum, broncho- pneumonia, hemorrhagic pancreatitis, necrosis of the renal tubules, and severe adrenocortical atrophy)	--	--
Ohshima T et al. (1992) [21]	52-day-old female	Heat stroke death caused by an electric kotatsu (a Japanese electric foot warmer with a coverlet) and overlapping clothing and blankets. The death was confirmed less than one hour after admission to hospital.	Axillary temperature of 41.3 °C.	First- and second-degree burns on the body. Face congestion.	Thoracic petechiae and ecchymosis scattered and variously distributed (in the thymus gland, on the pleura, on epicardial surface, on the serosa of large vessels, on the inner surface of the rib cage, and on the diaphragm). Additional subendocardial hemorrhages in the left ventricle.	Multi-visceral congestion, brain, and myocardial edema. Lungs: interstitial edema and emigration of the erythrocytes and the macrophages.	--
Donoghue ER et al. (1997) [5]	Two 3-year-old male children.	Heat stroke deaths of two boys found collapsed in a car. In both cases, the death was noted within 1 h of discovery.	Rectal T was 41.7 °C and 42.2 °C.	Unremarkable.	Brain edema and multi-visceral petechial hemorrhages (heart, lungs, and thymus gland) in both cases. Extensive lung hemorrhage in one case.	--	--
	37-year-old man	Heat stroke death in man found dead in his car with alcohol intoxication.	Rectal temperature was 41.9 °C.	Skin slippage and multiple bruises.	Moderate coronary atherosclerosis. Fatty liver. Lung and spleen congestion.	--	High level of blood alcohol concentration.
Zhu BL et al. (1998) [22]	9-month-old female	Heat stroke death during sleep caused by confinement under a blanket and a thick quilt.	--	Unremarkable.	Many petechial hemorrhages in the upper chest and thoracic viscera. Concentrated blood, sign of dehydration.	Histological and immunohistochemical investigation revealed signs of shock and myolysis in the cardiac and skeletal muscles.	--
Nadesan K et al. (1998) [23]	30-year-old woman.	Heat stroke collapse during jungle trekking. She died about 8 h after admission to hospital.	At time of admission, the axillary temperature was 40 °C.	Irregular areas of skin bruising.	Blood-stained bubbly fluid in the trachea and bronchi. Areas of hemorrhage in the mucosa of the upper airways and gastrointestinal tract. The stomach and the intestine contained blood-stained fluid. Subpleural and subendocardial hemorrhages. Pulmonary congestion and edema. Brain edema with subarachnoid hemorrhage on the right temporal area.	Severe pulmonary edema with extensive intra-alveolar hemorrhage and congestion of the blood vessels. Congestion of liver sinusoids.	Blood culture negative for microorganisms and toxicology tests negative for abuse substances.
Ng’walali PM et al. (1998) [24]	54-year-old man.	Heat stroke death in a vehicle. The body was found in the driver’s seat of the car with the engine running and with the heating at maximum power and speed.	Rectal temperature of 43 °C at 10 h postmortem.	Several superficial skin burns.	White bubbly fluid in the trachea and bronchi. Lung congestion and hemorrhages. Enlarged liver with micronodules on the surface.	Pulmonary congestion and edema. Alcohol-induced micronodular cirrhosis of the liver.	Gas chromatography revealed increased alcohol concentrations.
Green H et al. (2001) [25]	Eight men and a woman with ages ranging from 21 to 77 years old.	Nine cases of heat-related deaths of people exposed to high environmental temperature in South Australia.	--	Skin burns with blistering in 2 cases.	Advanced state of decomposition in 5 cases Micronodular cirrhosis in 1 case. Cerebral atrophy in 1 case.	--	In 1 case, a high blood alcohol level was detected.
Krous HF et al. (2001) [26]	Children aged 53 days to 9 years.	Eight bodies were found in vehicles and two in beds. Three of them were found dead and seven died within an hour of admission to the hospital.	The body temperature was only detected in six of them and was between 37 and 42.2 °C	Dehydration signs in 5 cases. Cutaneous petechiae in 2 cases, early skin slippage in 2, and skin burns in 1. The skin “felt like 200 degrees” in 1 case.	Intrathoracic petechiae in 9 out of 10 cases. Signs of contusion and non-fatal cerebral bleeding in cases where the manner of death was deemed homicide.	Severe pulmonary hemorrhage in 1 case. Skeletal muscle necrosis in 1 case. Hepatic centrilobular degeneration in 1 case. Acute splenitis in 2 cases.	--
Schuliar Y, et al. (2001) [27]	A male child and a female child of 5 and 3 years old.	Heat stroke death in a confined and unventilated environment (car).	The rectal temperature was 41.6 8 °C for the boy and at 40.8 °C for the girl.	Marblings and vesicles on the body, dehydration signs, and a whitish foam on the lips.	Unremarkable except for empty bladder and small quantity of blood in the vessels.	Pulmonary edema.	--
Rav-Acha M et al. (2004) [28]	Six men of about 20 years old.	Heat stroke collapses during military infantry training. The interval from time of collapse to time of death varied from 30 min to 72 h.	--	Unremarkable.	Multi-visceral congestion, edema, hemorrhages in all cases. Peritoneal infiltrate in 1 case, massive hepatic necrosis in 1 case.	--	--
Fineschi V. et al. (2005) [29]	8-day-old male infant	Heat stroke death in an incubator.	--	Second-degree skin burns, signs of dehydration and erythema.	Petechial hemorrhages on the pericardial, epicardial, and pleural surfaces. Congestion and pulmonary edema.	Histological signs suggestive of second-degree skin burns. Tracheal de-epithelialization and nuclear elongation of residual cellular elements. Pulmonary findings of edema, hemorrhages, acute stasis, and acute emphysema; sloughed-off epithelial cells and moderate eosinophilic amorphous material in the bronchial lumen.	Positive results from the immunohistochemical reaction for HSPs (anti-heat shock proteins) 90, 70, and 27 on tracheal and skin sections as sign of heat injury.
Byard RW et al. (2005) [30]	37-year-old male	Dehydration and heat-related death in a “sweat lodge” during a purification ceremony.	--	Scattered skin lesions consistent with superficial burns.	Unremarkable.	Unremarkable.	--
Zhou Y et al. (2006) [31]	41-year-old man	Heat stroke death caused by electric blanket.	Rectal temperature of 41.2 °C.	Diffuse second-degree burns and skin erythema on the chest.	Brain congestion and edema. Spleen and kidney congestion.	Heart: focal contraction bands, with some interstitial lymphocytes. Lungs: alveolar edema and hyperemia. Liver: fatty degeneration, with focal vacuolar change (ballooning) in the hepatocytes, scattered hepatocyte necrosis, and nonspecific portal lymphocyte infiltrations. Kidney: protein casts in the renal tubules and vascular congestion.	--
	13-year-old girl		Rectal temperature of 41 °C.	Diffuse second-degree burns on the body.	Multi-visceral congestion and edema.	Unremarkable.	--
Roccatto L et al. (2010) [32]	19-year-old worker	Heat stroke collapse in a worker. He died due to multiple organ failure 36 h after admission to hospital.	43 °C at time of admission to the hospital.	Unremarkable.	Unremarkable.	Cerebral and pulmonary edema, diffuse hemorrhages.	Urine and blood toxicological tests negative for abuse substances.
Gómez Ramos MJ et al. (2012) [33]	20-year-old man	Heat stroke collapse while working in the sun in a man with history of obesity, hypertension, and schizophrenia. He died 9 h after admission to hospital.	On admission to hospital, rectal temperature was 41.8 °C.	Skin burns with epidermal loss scattered on the body.	Congestion and hemorrhages of upper airways and lungs.	Multi-visceral congestion and petechial hemorrhages. Brain edema. Subendocardial necrosis of the renal tubules.	--
Alunni V. et al. (2015) [34]	6-year-old boy	Heat stroke death caused by confinement in an unpowered icebox in the absence of environmental hyperthermia.	Anal temperature of 34 °C (3:30 h after his discovery).	Signs of bleeding in the orifices of the face and cyanosis. Bruising from attempts to exit the icebox.	Congested and edematous lungs and cerebral edema.	Acute pulmonary emphysema with alveolar distension and rupture of the interalveolar septa. Food traces in the bronchi and bronchioles. Few signs of anoxic lesions in the brain.	High myoglobin level and low levels of ACTH in peripheral blood. Sodium and chloride concentrations in the vitreous humor 142 and 123 mmol/L (normal values < 145 and <105, respectively). Pathophysiology studies showed that the death was not due to lack of oxygen or excess CO2.
Adato B et al. (2016) [35]	Eight children with ages ranging from 7 months to 6 years old	Fatal heat stroke in eight children found dead in parked cars.	--	First- and second-degree burns in 3 cases, abrasion of the forehead in 1 case.	Visceral and/or serous membranes and petechial hemorrhages in 9 cases. Multi-visceral congestion in 1 case and lung congestion in 3 cases. Acute pneumonia in 1 case. Acute emphysema in 1 case. In 1 case, no autopsy was performed.	--	--
Nadesan K. et al. (2017) [36]	25-year-old male	Heat stroke death during a music festival, aggravated by the intake of MDMA. Found dead.	--	Signs of dehydration.	Multi-visceral congestion and edema. Epicardial hemorrhages.	Unremarkable.	--
	21-year-old male	Heat stroke death during a music festival, aggravated by the intake of MDMA and ketamine. He died one hour after admission to hospital.	Body temperature of 41.4 °C.	Unremarkable.	Multi-visceral congestion. Lungs heavy, congested, and with subpleural hemorrhages. Epicardial and sub-endocardial hemorrhages. Gastric mucosa hemorrhage and gastric lumen containing hemorrhagic fluid material.		--
	21-year-old female	Heat stroke death during a music festival, aggravated by the intake of MDMA. He died six hours after admission to hospital.	Body temperature of 38.9 °C.	Many skin bruises and extrusion of watery stools with bleeding from the anus.
Fais P et al. (2018) [37]	31-year-old man	Heat-stroke-related death of a man found dead inside a locked car.	Rectal temperature of 40 °C.	Unremarkable.	The body was in an initial stage of decomposition. Multi-visceral congestion. Petechial hemorrhages on the surface of the lungs and white foamy fluid in the bronchi.	Foci of liver centrilobular necrosis and tubular necrosis in the kidneys.	Urinary enzyme immunoassay positive for morphine. Tests made it possible to exclude acute fatal drug intoxication. Urine myoglobin concentration 3600 ng/mL (clinical normal range: 0–1000 ng/mL).
	47-year-old man	Heat-stroke-related death of a man found dead locked inside a car with an empty blister pack of benzodiazepines, two insulin pens, a suicide note, and a blood-stained folding knife.		Hesitation marks and superficial stab wounds on both wrists with little bleeding, devoid of lethal power.	--	Multi-visceral congestion.	Enzyme immunoassay on vitreous humor positive for benzodiazepines. Tests made it possible to exclude acute fatal drug intoxication. Increased sodium and chloride levels in vitreous humor.
	57-year-old man	Heat-stroke-related death of a man found dead inside a locked car with an empty blister pack of benzodiazepines and a suicide note.	--	Unremarkable.	Dilation of the right cardiac cavities.	Inconclusive for advanced state of decomposition.	Positive toxicological tests for benzodiazepines. Tests made it possible to exclude acute fatal drug intoxication.
Bazille et al. (2005) [38]	63-year-old man	Heat-stroke-related death of a man discovered unconscious outdoors with generalized seizures. He had chronic alcoholism and schizophrenic psychosis treated with olanzapine. He died from multiorgan failure 28 h after admission.	On admission to hospital, the temperature was 43 °C.	-	-	Acute cerebellar lesions with vacuolation of the myelin sheath, which was particularly striking around the dentate nuclei.	Laboratory tests showed an elevated serum lactate, a mild elevation in plasma creatinine, and a decreased platelet count. Routine toxicologic screening was negative. Positive results from the immunohistochemical reaction for HSP-70 in the cerebellar cortex.

.

As our review showed, heat stroke death and heat-related death occur frequently in infants during sleep due to overlapping of clothing and blankets and/or exposure to high environmental temperature [17,22]. Our review also confirmed that fatal heat stroke is common in children who are forgotten in parked vehicles, especially on warm days and under the rays of the sun [5,26,27,35]. Zhou Y et al. and Ohshima T et al. described cases of HS deaths resulting from electric blankets use [21,31]. Fineschi et al. reported a unique case of an 8-day-old male infant found dead in an incubator from a heat stroke [29]. Only Alunni V. et al. [34] described a case of fatal heat stroke of a child confined inside an unpowered icebox in the absence of environmental hyperthermia. To assess the diagnosis of heat stroke death, the authors performed physiological experiments, which suggested that death by asphyxia was less likely. Instead, the review showed that heat-related deaths of adults are more frequently due to intense physical exertion with high ambient temperatures. In fact, the literature describes heat-related deaths occurring during or after intense physical exercise [18,19,23], strenuous working [20,32,33], military training [28], or high-intensity recreational activities [36]. In addition, in many heat-related cases, death was associated with alcohol or drug intake [24,25,36] which was sometimes considered a contributing factor to death [5,36]. Finally, the literature describes cases of heat-related deaths in circumstantial data suggestive of suicide [37].

The deceased was elderly in only one case [25]. To the best of our knowledge, there are no cases in literature of heath stroke deaths of elderly people suffering from dementia. It is also noteworthy that in most cases there were circumstantial elements which suggested a heat-related death. This showed that, in the absence of such elements, the diagnosis of heat stroke death is very complex.

There are no cases of elderly people who died in circumstances like those we have described. This result is probably because in elderly people, in cases of suspected heath stroke death, comorbidities coexist more frequently and must be excluded as alternative causes of death. Therefore, in these cases, heat stress is more often considered not as the cause of death but as a contributing condition to death. Conversely, in our case, heat stroke can be considered the only cause of death, which is also because there are no other alternative pathologies with causal value. This was demonstrated both by the woman’s medical history and by the absence of significant autoptic, histological, and toxicological findings.

As in our case, the body temperature was not available in many cases [16,17,22,25,28,29,30,35,36,37]. In other cases, the body was found in a state of decomposition, which does not allow body temperature measurement [25,37]. This detection was more reliable in cases where the death occurred in hospital [18,19,20,21,23,26,28,33,36,38].

Moreover, our study confirmed that the body temperature is dependent on the duration of exposure to heat and the time between collapse and death and between death and discovery of the body.

Relative to the external examination, the most frequent finding concerns skin burns of varying degrees [21,24,25,26,29,30,31,33,35], notably represented in cases of direct skin exposure to heat sources (such as electric blankets [21,31] or incubators [29]) or prolonged exposure to sunlight (as in the case of people found dead in parked cars [24,26,35] or working in the sun [33]). In addition, dehydration signs [26,27,29,36] are present in many cases and skin bruises in some others [5,36]. Even in our case, the corpse skin unprotected by clothing showed signs of superficial sunburns. In addition, in most cases described, there were no injuries or signs of violence on the body, as in our case.

The literature review confirmed that heath stroke deaths are not associated with autoptic or histological pathognomonic findings, particularly if the survival interval is short [39,40]. Postmortem signs are mostly nonspecific and due to antemortem agony, organ failure, and hemorrhagic diathesis, the ultimate causes of heat death.

Indeed, the most recurrent autopsy results are petechial visceral and serous hemorrhages mostly localized in the thoracic region [5,17,21,22,26,29,33,35,36,37] and confirmed by a histological examination. In our case, the autopsy showed widespread hemorrhage petechiae in many of the organs examined (lungs, stomach, spleen, and kidneys). Other nonspecific macroscopic findings were congestion and multi visceral edema.

Our review also showed that histological findings often merely confirmed gross results. However, in some cases, histological examinations detected renal tubular necrosis [18,20,33,37] and hepatic necrosis [28,31,37]. Signs of myolysis or muscle necrosis were found in only two cases [22,26]

In our case, the histological examination was capable of detecting microscopic signs of acute pulmonary emphysema (alveolar distension and rupture of the interalveolar septa). These histological findings—which require a differential diagnosis with asphyxia dynamics—are remarkable because they have been found only in one other case in the literature [34].

In our case, histological examinations confirmed the infiltration of erythrocytes into the tissues where gross hemorrhages were found. The kidneys showed signs of acute tubular necrosis and infiltration of neutrophil granulocytes. Our histological results are consistent with a heat stroke survival time of <12 h [41].

As our review has shown, only rarely have biochemical and physiological investigations been employed for the diagnosis of fatal heat stroke. Only in two cases was the level of myoglobin measured in blood and/or urine [34,37], and only in one case was the level of pituitary hormones measured in peripheral blood [34].

Finally, it is important to highlight the low use of immunohistochemical investigations aimed at postmortem detection of HSPs (heat shock proteins) [16,29,38]. Bazille et al. [38] described three heat-related deaths, highlighting the inverse correlation between survival time of the subjects and the brain expression of HSPs. In fact, the expression of HSP was highest in the cerebellum of the case where the subject died 28 h after heat stroke. It was mild in the case where the subject died 1 month after the heat stroke, and absent in the case where the subject survived for 2 months after the heat stroke. Wegner et al. [16] described two sauna-associated deaths and showed that, despite vital heat exposure, in the first case, no expression of HSPs was found. The authors hypothesized that this could be due to a genetic polymorphism which could have an influence on the grading of the immunohistochemically visualized heat shock protein.

In our case, the expression of HSPs was detected in the skin tissues, potentially suggestive of the exposure of the woman to very high temperatures when she was still alive. So, this immunohistochemical result—together with the circumstantial, autoptic, and toxicological findings—has contributed to the diagnosis of the cause of death.

To conclude, our study confirmed that the forensic diagnosis of heat-related deaths is based on a set of multiple data obtained from on-site inspection and study of the circumstantial data, autopsy, and toxicological examination. These data—already unspecific—are not always available, with the risk of underestimating this type of death. Especially considering that the diagnosis is still made by exclusion, it is crucial that all these data are collected accurately. Especially in cases like ours where the diagnosis is particularly complex, it is also essential to conduct a thorough investigation of the clinical history of the subject. Finally, immunohistochemical investigations are still poorly applied in such death circumstances, although they represent a tool of investigation of undoubted utility.

4. Conclusions

Our study results highlighted the complexity of diagnosing heat stroke deaths. In view of the little use of immunohistochemistry demonstrated by our review, further studies are needed to elucidate the role of HSPs in forensic diagnosis of heat-related deaths. This will be essential to understanding the actual forensic usefulness of HSP detection in these circumstances. Our study is far from conclusive in this respect but, in our opinion, can be a valid starting point.

In heat stroke deaths, there are no specific signs that allow immediate diagnosis without further investigation. On the contrary, diagnosis is the result of a set of analyses, each of which makes an important contribution. As proved by our case, the medical history of the subject and circumstantial data can help to shed light on the dynamics of death. Especially when the cause of death is suspected and there are no alternative causes of death, immunochemical investigations for specific proteins released from high temperature exposure (HSPs) may also be useful.