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Rev Clin Esp. 2020;xxx(xx):xxx---xxx

Revista Clínica
Española
www.elsevier.es/rce

REVIEW

Acute, subacute and chronic mountain sickness夽

E. Garrido a,d,∗ , J. Botella de Maglia b,d , O. Castillo c

a
Servicio de Hipobaria y Fisiología Biomédica, Universidad de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain
b
Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, Spain
c
Instituto Nacional de Biología Andina, Universidad Nacional Mayor de San Marcos, Lima, Peru
d
Instituto de Estudios de Medicina de Montaña (IEMM), Barcelona, Spain

Received 16 October 2019; accepted 16 December 2019

KEYWORDS Abstract More than 100 million people ascend to high mountainous areas worldwide every
Altitude; year. At nonextreme altitudes (<5500 m), 10---85% of these individuals are affected by acute
Monge’s disease; mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia.
Pulmonary Approximately 140 million individuals live permanently at heights of 2500---5500 m, and up to
hypertension; 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary
Hypoxia; hypertension) or the chronic form (Monge’s disease), the latter of which is especially common
Mountain sickness; in Andean ethnicities. This review presents the most relevant general concepts of these 3
Mountaineering. clinical variants, which can be incapacitating and can result in complications and become life-
threatening. Proper prevention, diagnosis, treatment and management of these conditions in
a hostile environment such as high mountains are therefore essential.
© 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights
reserved.

PALABRAS CLAVE Mal de montaña de tipo agudo, subagudo y crónico

Altitud;
Enfermedad de Resumen Más de 100 millones de personas ascienden cada año a áreas montañosas elevadas
monge; en todo el planeta, y en altitudes no extremas (<5.500 m) entre el 10-85% se ven afectados
Hipertensión por el denominado mal agudo de montaña, la patología más frecuentemente inducida por
pulmonar; una hipoxia hipobárica ligera-moderada. Asimismo, unos 140 millones de seres humanos viven
Hipoxia; de forma permanente en cotas comprendidas entre 2.500---5.500 m, y hasta un 10% de ellos
Mal de montaña; padecen la forma subaguda del mal de montaña (hipertensión pulmonar de la gran altitud)
Montañismo. o la forma crónica (enfermedad de Monge), esta última especialmente frecuente en etnias
andinas. La presente revisión expone los conceptos generales más relevantes en torno a estas

夽
Please cite this article as: Garrido E, Botella de Maglia J, Castillo O. Mal de montaña de tipo agudo, subagudo y crónico. Rev Clin Esp.
2020. https://doi.org/10.1016/j.rce.2019.12.013
∗ Corresponding author.

E-mail address: eduardogarrido@movistar.es (E. Garrido).

2254-8874/© 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

RCENG-1811; No. of Pages 9

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2 E. Garrido et al.
tres variantes clínicas, las cuales pueden ser incapacitantes, llegar a complicarse y ser
potencialmente mortales, siendo esencial el realizar una correcta prevención, diagnóstico,
terapéutica y manejo de las mismas en un entorno hostil como es la alta montaña.
© 2020 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). Todos los
derechos reservados.
Background
It is estimated that 5% of the worldwide population per-
manently live in mountainous areas, and approximately 140
million of them live at high altitude (<2500m). Every year,
more than 100 million people visit or travel to high mountain
areas for professional, touristic, sports or religious reasons,
reaching high geographical heights through various means of
transportation or by performing intense physical activity.1
Barometric pressure falls dramatically as the altitude
increases, resulting in a reduced partial pressure of oxy-
gen and the ensuing drop in arterial oxygen pressure (PaO2 )
and oxygen saturation (SaO2 ). Health disorders caused by
this hypoxemia depend on the height reached, the speed of
ascent, the time spent at that height and the individual’s
physiological response (known as acclimatization).2 This
biological process launches adaptive phenomena in various
organs and systems3 by stimulating complex oxygen-sensing
mechanisms4 that activate the hypoxia-inducible factor,
transcription factor for the expression of numerous genes
that regulate oxygen deprivation and tissue homeostasis.5
Nevertheless, humans can only adapt to extreme altitudes
(<5500m) for brief periods.6 Considering that the mean PaO2
and SaO2 values above 8000 m are below 35 mm Hg and
70%, respectively,7,8 a state of coma would occur within
3 min in the absence of acclimatization.9 When the degree
of acclimatization to hypoxia is inadequate for a certain
altitude, a varied spectrum of dysfunctions and health dis-
orders occur,3,10 with mountain sickness the most common
condition experienced. Depending on the symptom onset,
characteristics and progression, the disease can be classi-
fied into 3 well-differentiated forms or types, which do not
correspond to different pathochronic stages of the same
clinical entity. These types are called acute mountain sick-
ness (AMS), subacute mountain sickness (SMS) and chronic
mountain sickness (CMS). Table 1 shows the main differences
between the types.
Acute mountain sickness
Although there are old symptomology descriptions, this
disease was clinically classified in 1913 by the British doc-
tor Thomas Ravenhill.11 The exact pathogenic mechanism
is still not well understood; however, encephalic vasodi-
lation, vasogenic edema, increased intracranial pressure
and meningeal distension appear to be the most feasible
mechanisms.12 High-altitude cerebral edema (HACE) corre-
sponds to a progressed stage of AMS, and although the form
by which it progresses from one stage to another is contro-
versial, it appears to be due to a failure in the blood-brain
barrier due to a mechanical or cytotoxic aggression or diffi-
culty draining the cerebral venous flow.13
Clinical presentation
AMS typically occurs at altitudes higher than 2500 m but can
occur around 2000 m. The higher the altitude, the higher
the incidence and intensity of AMS symptoms, affecting
10---25% of nonacclimated individuals who ascend to heights
of approximately 2500 m and 50---85% of those who ascend
to altitudes of 4500---5500 m.14 The mean incidence rate of
AMS increases by approximately 13% for each 1000 m above
2500 m.15 The clinical manifestation is typically nonspecific:
isolated headache or accompanied by asthenia, anorexia,
nausea, vomiting, lightheadedness and dizziness. Occasion-
ally, there is concomitant facial and peripheral edema,
especially in women, although it is not considered pathog-
nomonic of AMS. The symptoms usually start in the first
6---12 h and worsen as the individual gains altitude. The
diagnosis is performed exclusively by the symptoms. There
are several scoring systems for assessing the symptoms,16
although the most recommended for use by medical per-
sonnel is the Lake Louise scale,15,17 which correctly types
the patient through the presence and degree of impair-
ment of 4 essential symptoms (Table 2). A total score ≥3,
in the presence of headache, is considered diagnostic for
AMS; however, a score of 3 in the headache intensity, even
without other accompanying symptoms, is also diagnostic
for this clinical entity. Headache is therefore an essential
symptom in the manifestation of AMS, but the absence of
headache does not rule out the diagnosis, which is con-
firmed in this case with a total score ≥5. Severe cases are
usually completely incapacitating for most activities.17 In
children, especially in preverbal stages, AMS should always
be suspected in the presence of irritability and behavioral
changes. Headaches are usually pulsatile, worsen with phys-
ical exercise and the Valsalva maneuver, frequently start
during the first night and are quickly relieved by inhaling sup-
plemental oxygen. Any headache that starts after the third
day while staying at the same altitude of >2500 m should not
be attributed to AMS. Sleep disorders, very common at high
or extreme altitudes due to the onset of periodic breathing,
do not have a strict correlation with AMS.18 Nevertheless,
there does appear to be an association between this dis-
ease and the presence of subclinical high-altitude pulmonary
edema.19
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Table 1 General aspects and main differential characteristics of the 3 types of mountain sickness (the subacute type is also
called high-altitude pulmonary hypertension, while the chronic type is called Monge’s disease).

Types of mountain sickness Acute Subacute Chronic

Minimum altitude required 2000---2500 m 2500---5500 m 2500---3000 m
Risk population Children/adults Children/adults Adults
Time to symptom onset Hours Weeks/months Years
Predominant symptoms Cephalic Respiratory Neuropsychological
Gastrointestinal Cardiac Cardiopulmonary
Vascular
Clinical assessment Lake Louise scale Clinical presentation Qinghai scale
Hematocrit Normal ↑/↑↑ ↑↑↑
SaO2 ↓/↓↓ ↓/↓↓ ↓↓↓
PaCO2 ↓/↓↓ ↓ ↑↑↑
Pulmonary arterial pressure Normal/↑ ↑↑↑ ↑↑/↑↑↑a
Clinical course Self-limiting CHF CHF
HACE
Effective drugs Ibuprofen Nifedipine Enalapril
Acetazolamide Sildenafil Acetazolamide
Dexamethasone Medroxyprogesterone
Therapeutic alternatives Oxygen Oxygen Phlebotomy bleeding
Hyperbaric chamber Altitude loss Hemodilution
Altitude loss Oxygen
Altitude loss
Abbreviations: CHF, congestive heart failure; HACE, high-altitude cerebral edema; PaCO2 , partial pressure of carbon dioxide; SaO2 ,
arterial oxygen saturation.
a Occasionally normal or slightly increased.

The differential diagnosis should be performed with
migraine, exhaustion, dehydration, sunstroke, viral syn-
drome and alcohol or carbon monoxide poisoning.13 The
prognosis is good because the condition is typically self-
limiting during the first 4 days of staying at a same altitude.
Below 5000 m, less than 1% of cases of AMS progress to HACE,
an entity that should be suspected in the minimal presence
of cognitive disorder and the onset of ataxia 24---72 h after
the start of AMS.20 HACE is a medical emergency because
the onset of coma can occur within a few hours and can be
fatal due to brain herniation.14
as well as night-time oxygen therapy (0.5−1 L/min) are
highly effective for moderate AMS. When faced with severe
cases and minimal clinical suspicion of progression to HACE,
the treatment should consist of urgently descending the
patient, administering oral or parenteral dexamethasone
at a rate of 4 mg/6 h (after an initial dose of 8 mg) until
symptom remission. Oral acetazolamide (250 mg/12 h) can
be added, although corticotherapy is the main drug indica-
tion in these cases. If evacuation is delayed, oxygen may also
be administered (2---4 L/min) or recompression therapy may
be started in a portable hyperbaric chamber, attempting to
keep SaO2 at levels >90%.3,13,14,21

Treatment
In general, it is advisable to employ conservative measures,
stopping the ascent until the symptoms have spontaneously
remitted, although oral ibuprofen (600 mg/8---24 h) is indi-
cated to treat the headache, as well as oral or parenteral
ondansetron (4 mg/4---6 h) to treat the nausea and vomit-
ing. If, during the first 4 days, there is no improvement, the
individual must descend to an altitude 300---1000 m lower
or reach the previous height where the patient was asymp-
tomatic. The most incapacitating cases should be treated
with oral acetazolamide (250 mg/12 h) or oral or parenteral
dexamethasone (4 mg/6 h). The treatment regimen for chil-
dren for these drugs is 2.5 mg/kg/12 h (maximum 250 mg
per dose) and 0.15 mg/kg/6 h, respectively. Acetazolamide
is most effective for treating mild-moderate AMS, while
dexamethasone is most effective for moderate-severe AMS.
Either of both drugs should be stopped as soon as the symp-
toms disappear. Recompression using a hyperbaric chamber,
Prevention
The best strategy consists of acclimatizing to the altitude
progressively, ascending a daily slope of <500 m if overnight
stays at altitudes >2500---3000 m are planned, and devoting
a day to rest for every 3---4 days of new altitude gain.13,21
Caution is recommended for those individuals with a history
of migraine or deficient altitude adaptation, given that they
are more susceptible to high altitude headache and AMS.21,22
Chemoprophylaxis is only indicated for especially suscep-
tible individuals or when faced with scheduled overnight
stays at high altitude without possible acclimatization
and consists of oral acetazolamide (125 mg/12 h) or, in
rare cases, oral dexamethasone (2 mg/6 h or 4 mg/12 h).
Dexamethasone is reserved for when acetazolamide is con-
traindicated or is poorly tolerated. The combination of
the 2 drugs or even higher dosages of dexamethasone
(4 mg/6 h) may be considered exclusively in highly justified
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Table 2 Lake Louise scale for diagnosing and qualifying the
symptoms of acute mountain sickness.
Headache
0: absence
1: mild
2: moderate
3: intense (incapacitating)
Gastrointestinal symptoms
0: absence
1: anorexia
2: nausea or vomiting
3: nausea and vomiting (incapacitating)
Fatigue/asthenia
0: absence
1: mild
2: moderate
3: intense (incapacitating)
Dizziness
0: absence
1: mild
2: moderate
3: intense (incapacitating)
No diagnosis or doubtful AMS, score 1---2; mild AMS, score 3---5 (in
the presence of headaches); moderate AMS, score 6---9; severe
AMS, score 10---12.
Based on Roach et al. and the Lake Louise AMS Score Consensus
Committee.17 .
cases for rapid ascents by air to altitudes >3500 m and with
planned physical activity, such as is the case for military
missions and rescue teams.21 Typically, chemoprophylaxis
is started 8---24 h prior to the ascent, extending it by at
least 2 days if the individual remains at the same high alti-
tude but not exceeding 7---10 days of continuous regimen
if the individual keeps gaining altitude. Within these time
intervals, the chemoprophylaxis should not be discontin-
ued. Chemoprophylaxis should only be stopped once the
descent has started or during the descent.13,14,21 In children,
prophylaxis with dexamethasone is not indicated, and the
acetazolamide dosage is identical to the therapeutic dosage,
although it is only considered in justified cases and never for
infants. Chemoprophylaxis is absolutely not recommended
for extremely high altitudes, given that it can entail fatal
consequences.13
Other preventive strategies, such as sessions for inhal-
ing mixtures of hypoxic gases prior to an ascent to high
altitudes, have shown their effectiveness, although there
is no well-established preacclimatization protocol. Regard-
ing the chewing or infusion of leaves from the coca bush (a
widespread custom among visitors to some Andean regions),
there are no substantial studies that support this practice as
prophylaxis. Ginkgo biloba extracts have also failed to show
consistent effectiveness in the randomized studies. An abun-
dant intake of liquids does not have a preventive effect,
although proper hydration is important because dehydra-
tion can simulate AMS.21 Isolated SaO2 monitoring by pulse
oximetry during stays at high altitude can indicate if we
are within the normal range of this parameter at different
altitudes23 ; however, the use of this monitoring as a pre-
dictor of AMS is controversial.24 Certain sophisticated tests
that assess cardiopulmonary function through normobaric
hypoxia or in hypobaric chambers do help detect patients at
risk.25,26 Physical training has not been shown to have a pro-
tective effect against AMS,27 and vigorous physical exercise
performed at high altitude can promote the onset of AMS.28
Women, younger people, smokers, or overweight individuals
appear to have a higher susceptibility to AMS.29
In general, the risk of presenting AMS is very high when
exceeding the altitude of 3500 m in a single day, as occurs in
locations highly frequented by tourists and rapidly reached
by car, air, cable car or train. The concomitance of diseases,
especially cardiopulmonary, can also represent a contraindi-
cation for reaching altitudes >2500 m. Each case should be
assessed according to the altitude goal, type of ascent,
length of stay at altitude, activity envisaged, geographical
region and possibility of health care.30
Subacute mountain sickness (high-altitude
pulmonary hypertension)
The presence of pulmonary hypertension in high-altitude
residents was noted in 1932 by the Peruvian doctor Alberto
Hurtado.31 In 1962, other compatriots detected the presence
of right ventricular hypertrophy in native Andean children.32
Chinese physicians had already known of this disease in Asian
children, known as high-altitude heart disease; cases were
subsequently reported in adults in Tibet.33,34 More recently,
Soviet scientists studied patients with cor pulmonale in the
Pamir mountains.35 Despite these pioneers, the pediatric
form of this disease was not clinically described until 1988
when a study was conducted on Chinese children younger
than 16 months who had been transferred to Tibet and who,
after 2 months of living in Lhasa (altitude of 3656 m), devel-
oped severe pulmonary hypertension and congestive heart
failure and subsequently died. Their autopsies revealed right
ventricular hypertrophy and thickening of the tunica media
of the pulmonary arterioles. The clinical condition was
called SMS.36 In 1990, the condition was clinically described
in adults, specifically in Indian soldiers who lived for weeks
or months at 5800---6700 m in the Himalayas. The individuals
presented heart failure, right ventricular growth, increased
pulmonary vascular resistance and tricuspid regurgitation,
abnormalities that disappeared over the course of days or
weeks after the soldiers descended from the mountains.37
Clinical presentation
SMS is compatible with rapidly progressing congestive heart
failure because it manifests after weeks or a few months
of continuous exposure to high altitude. Its pathogene-
sis is through alveolar hypoxia, which causes immediate
and reversible pulmonary vasoconstriction, mediated by
endothelin-1 and other substances. If the hypoxia persists,
the pulmonary hypertension is maintained because over
time the tunica media of the pulmonary vessels thickens
due to the increase in its muscle component.38 The right
ventricle dilates and hypertrophies, and if the pulmonary
hypertension is very intense, the right ventricle claudi-
cates. The symptoms manifest as dyspnea, cough, cyanosis,
jugular venous distention, facial and lower limb edema, hep-
atomegaly, ascites, pericardial effusion and effort angina. In
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young children, symptoms can start nonspecifically as irri-
tability, lethargy, anorexia and insomnia. The incidence rate
for SMS is higher in children than in adults and higher in
male individuals, with cases reported in children and adults
at altitudes somewhat below 3000 m. As with the Quechua
and Aymara of the Andes, virtually all other humans present
pulmonary hypertension secondary to hypoxia as the mech-
anism for optimizing the ventilation/perfusion ratio and are
therefore potentially at risk of SMS during long exposures
to high altitude. Only Tibetans have a very low incidence
of SMS,39 given that they present no or minimal pulmonary
hypertension in hypoxia40 and therefore do not develop
cor pulmonale. This low incidence is believed to be due
to a natural selection process from exposure to a hypoxic
atmosphere, a process that has lasted millennia and has
remained relatively unchanged by miscegenation. Special
phenotypic, physiological and genetic adaptations explain
why ethnicities of Tibetan lineage are the best human model
for long-term adaptation to environmental hypoxia, given
that they provide the longest evolutionary anthropological
scale for permanent living at high altitude.41 Nevertheless,
permanent human life is not possible above 5500 m,6 mainly
because of SMS and muscle atrophy at high altitude.42 At
the Chilean mine of Aucanquilcha (5800 m), adjacent bar-
racks were constructed to avoid having miners ascend daily
from a nearby town; however, within a few months, all of
the miners became sick and unable to work.43
The fact that SMS occurs in adults at altitudes typically
above 5500 m and in infants at altitudes above 2500---3000 m
is due to the fact that children develop greater hypoxic
pulmonary hypertension, given that the pulmonary vaso-
constrictor response to hypoxia tends to decrease with
age.44 The current criterion for considering high-altitude
pulmonary hypertension excessive is a systolic pulmonary
arterial pressure >50 mm Hg or a mean pressure >30 mm
Hg for adults and a systolic pressure >65 mm Hg for chil-
dren younger than 6 months.45 Nevertheless, SMS can
typically be diagnosed in adults noninvasively by the symp-
toms, through electrocardiography, chest radiology and
echocardiography.45,46 Pediatric cases diagnosed by echocar-
diography have recently been reported.47
Treatment and prevention
Adults should avoid long stays at altitudes higher than
5500 m, and non-Tibetan children younger than 12 months
should not be transferred to areas above 3000 m for
extended periods, given that sudden death can occur after
only presenting nonspecific pediatric symptoms for a few
weeks. Some adults improve temporarily with supplemental
oxygen,46 as well as with nifedipine or sildenafil,3 although
full remission of SMS (in children and adults) is only achieved
by descending to low altitude.38
Chronic mountain sickness (Monge’s disease)
In 1925, the Peruvian doctor Carlos Monge first described
polyglobulia in a native Andean, subsequently confirming
this finding in other Andeans.48 CMS is currently defined as
a clinical syndrome that occurs in long-term residents of
high-altitude areas (>2500 m) and is characterized by exces-
5
sive erythrocytosis and hypoxemia.45 The concept of loss
of high-altitude adaptation secondary to idiopathic cen-
tral hypoventilation (primary CMS) has been accepted as the
etiopathogenic mechanism; however, the presence of conco-
mitant diseases can promote CMS (secondary CMS),49 and
a phenomenon of adaptation to disease in a hypoxic envi-
ronment can also be a valid concept.50 In both contexts,
CMS does not correspond to a single entity, given that it
can coexist with lung disease, heart disease, nephropathy,
hemoglobinopathy and with metabolic disorders, hormonal
disorders, carotid body disorders, cobalt in blood and pul-
monary thromboembolism.3,49,51 In recent years, a possible
genetic predisposition to CMS in Andean ethnic groups has
been reported.52
The mean prevalence rate for CMS is 5---10% among
the global population who reside at altitudes higher
than 2500 m.45 Consequently, up to 14 million individuals
worldwide might have CMS. Nevertheless, this rate varies
according to the altitude of the place of residence and
among populations of various mountain regions. Cases have
been reported at only 2000 m of altitude53 ; however, the
highest incidence occurs above 3000 m, affecting 5---18% of
the residents of the Andes,54 14---29% of the residents of
certain areas of the Indian Himalayas55,56 but only 1% of
native Tibetan residents.57 This lower prevalence can be
explained by the special adaptation to hypoxia that the
Tibetans possess,6,41 which was discussed earlier in the pre-
vious subsection. In general, the higher the altitude and the
longer the time residing at that altitude, the greater the risk
of CMS, which, starting in the sixth decade of life, can affect
a third of the population of certain Andean communities.58
Clinical presentation
Depending on the stage or progression of the disease,
patients can present dyspnea, palpitations, insomnia, loss
of appetite, joint pain, cyanosis, varicose veins in the
legs, acropachy, palmar erythema, epistaxis, conjuncti-
val injection and facial flushing (Fig. 1). In addition to
the congestive aspect that many patients usually show,
there are associated neuropsychological symptoms, such
as headaches, dizziness, tinnitus, peripheral neuropathy,
depression, confusion and amnesia.3,45,49,59---61 There have
been reported cases that even develop cerebral edema
and encephalopathy.62 Nevertheless, it is not uncommon to
detect asymptomatic patients who present excessive poly-
globulia in routine blood tests and SaO2 values <85%, even
at altitudes higher than 4000 m.49 CMS is more common
in men, especially of Andean ethnicity; however, a signif-
icant incidence has been reported in non-Tibetan women
who reside in the Himalayas.56 The Qinghai scale classi-
fies patients according to the degree of severity, thereby
establishing an overall score by scoring for the presence
and intensity of 8 essential symptoms and clinical signs,
as well as a hemoglobin concentration threshold of 21 g/dL
for men and 19 g/dL for women (Table 3).45,49,63 Patients
with CMS frequently have pulmonary arterial hypertension,
whose intensity and clinical manifestation can vary dra-
matically from one individual to another.3,59 In advanced
stages, there is remodeling of the pulmonary arterioles and
right ventricular hypertrophy/dilation.64 Ventricular failure
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Fig. 1 Chronic mountain sickness or Monge’s disease.

The images show some of the physical stigma of this disease, such as facial congestion, labial and nail bed cyanosis, watch-glass
nails and distal hyperpigmentation, palmar erythema, and varicose veins in the legs.
Images provided by Dr. Francisco C. Villafuerte.

is not typically produced, although its actual incidence
rate is unknown.65 There have also been reports of the
presence of systemic vascular dysfunction, which can predis-
pose patients to early cardiovascular disease.66 Despite the
hypoxemia, increases in hematocrit and subsequent blood
hyperviscosity, it has been observed that erythroblast apop-
tosis is reduced in these patients.67
Residents of high-altitude areas who present exces-
sive hematocrit levels should initially undergo examinations
with spirometry, chest radiology, electrocardiography and
echocardiography to assess pulmonary function and detect
signs of pulmonary hypertension and right ventricular
growth.50 Stress testing has demonstrated that the aer-
obic function during physical exercise appears to be
preserved despite these patients’ pulmonary hypertension
and relative hypoventilation.68 Nevertheless, physical activ-
ity can induce severe pulmonary hypertension in these
patients, with the rapid onset of interstitial pulmonary
edema and subsequently increased hypoxemia and exercise
intolerance.69 Pronounced pulmonary hypertension, even
during moderate physical exercise as part of daily activi-
ties, can be the origin of these patients’ greater morbidity
and mortality,70 whose death could be caused by congestive
heart failure or stroke.49 A number of vasoactive peptides,
such as B-type natriuretic peptide and endothelin-1, can
have an important role in the clinical expression of Monge’s
disease.71 Increased androgenic hormonal activity (given the
erythropoietic function of testosterone) can be related to
an excessive polyglobulic reaction in these patients.72 The
hypoventilation presented by these patients at rest could be
a defense mechanism given that it involves a lower energy
expenditure.73 Their hypoxemia during sleep is even more
pronounced than during their waking hours and has been
related to existing pulmonary and systemic vascular dysfunc-
tion; the presence of patent foramen ovale can promote
this hypoxemia.74 The increased formation of free radi-
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etin production secondary to renal or testicular tumors,

Table 3 Qinghai scale for diagnosing and qualifying the
testosterone treatments).
symptoms of chronic mountain sickness.
Dyspnea/palpitations
Treatment and prevention
0: absence
1: mild
2: moderate
Effective strategies include transferring the patient to
3: intense
a location at lower altitude, permanently administering
Insomnia
supplemental oxygen and attempting to keep the poly-
0: absence
globulia at an optimal compensation level.50 The first
1: mild
option achieves a decrease in polyglobulia in approximately
2: frequent wakings
3 weeks77 ; however, if the patient is transferred to a
3: absolute
tropical environment, their risk of pneumonia and asthma-
Cyanosis
like syndromes increases, especially in cases of secondary
0: absence
CMS. Many patients from the Andes and Himalayas would
1: mild
be forced to leave their jobs and their family’s finan-
2: moderate
cial support, with the subsequent severe social problem
3: intense
that this migration entails. The second option reverses
Varicose veins
many of the symptoms but handicaps the patient by mak-
0: absence
ing them oxygen-dependent and is counterproductive in
1: mild
CMS secondary to undiagnosed diseases. Oxygen therapy is
2: moderate
only effective in cases of severe CMS.78 The third option
3: intense
focuses on treating the underlying causes of the hypox-
Paresthesia
emia and, consequently, the polyglobulia. With good control
0: absence
of the underlying diseases, these patients’ life expectancy
1: mild
increases, avoiding the accelerated psychophysical impair-
2: moderate
ment and abandonment of the patients’ residence. Although
3: intense
they immediately reduce blood viscosity, palliative ther-
Headaches
apies through bloodletting and isovolemic hemodilutions
0: absence
induce metabolic disorders, exertional dyspnea and asthe-
1: mild
nia, if frequently applied, and are not recommended as
2: moderate
long-term therapy for these patients. Oral drug ther-
3: intense (incapacitating)
apy with medroxyprogesterone (60 mg/24 h), acetazolamide
Tinnitus
(250 mg/24 h) or enalapril (5---10 mg/24 h) also constitute
0: absence
effective therapeutic options,45,49,54,79 although there is no
1: mild
scientific evidence on their safety in very long-term therapy
2: moderate
for CMS. Nevertheless, the most severe cases should leave
3: intense
high altitudes or live at sea level,49 despite the fact that
Hemoglobin (concentration)
resting pulmonary hypertension in Andean natives can take
0: <21 g/dL (♂)
more than 2 years to normalize, and the pulmonary hyper-
3: ≥21 g/dL (♂)
tensive response to exercise can last indefinitely.80 Other
0: <19 g/dL (♀)
stigma such as varicose veins and acropachy also persist.
3: ≥19 g/dL (♀)
With a minimum clinical suspicion of CMS or patients who
might be at risk of CMS (sleep apnea, postmenopause, fam-
No diagnosis or doubtful CMS, score 1---5; mild CMS, score 6---10; ily predisposition), smoking cessation is essential, as well as
moderate CMS, score 11---14; severe CMS, score >15. preventing diseases of the respiratory system, excess body
Based on León-Velarde et al.45 , Villafuerte and Corante49 and
weight, malnutrition and iron deficiencies. Regular physical
Wu et al.63 .
exercise at moderate intensity substantially improves these
patients’ general condition, but strenuous physical activ-
cals and the reduced viability of nitric oxide are associated ity should be avoided. These patients should be evaluated
with rapid cognitive impairment and the onset of depres- annually.49
sive symptoms in these patients.75 Given that CMS symptoms
and clinical signs are aggravated with increases in altitude, Conflicts of interest
attempts have been made to quantify the normal polyglob-
ulic reaction for certain altitudes. For very high hematocrit The authors declare that they have no conflicts of interest.
levels (approximately 80%), a multifactorial mechanism
known as triple hypoxia syndrome was proposed (hypobaric
hypoxia + chronic hypoxia due to concomitant hypoxemic Acknowledgements
diseases + acute hypoxia due to superadded inflammatory
processes).76 In those cases of CMS where there is diag- The authors would like to thank Dr. Francisco C. Villafuerte
nostic uncertainty, other causes of polyglobulia should be (University Cayetano Heredia, Lima, Peru) for providing the
considered (e.g., polycythemia vera, excessive erythropoi- photographs.
+Model
ARTICLE IN PRESS
8 E. Garrido et al.
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