Journal of Clinical Gerontology & Geriatrics 6 (2015) 30e33

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Case report

Difculty in managing polypharmacy in the elderly: Case report and

review of the literature
Rhita Bennis Nechba a, b, *, Moncif El M'barki Kadiri c, Mounia Bennani-Ziatni d,
Amine Ali Zeggwagh e, Abdelhalim Mesoui b
a

Department of Medicine, El Idrissi's Hospital, Kenitra, Morocco

Laboratory of Genetics, Neuroendocrinology and Biotechnology, Ibn Tofal University, Kenitra, Morocco
Department of Nephrology, Dialysis and Transplantation, Military Hospital, Rabat, Morocco
d
Department of Chemistry, Ibn Tofal University, Kenitra, Morocco
e
Department of Intensive Care, Avicenne University Hospital, Rabat, Morocco
b
c

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 13 December 2013
Received in revised form
28 May 2014
Accepted 5 June 2014
Available online 26 August 2014

Elderly patients with multiple comorbidities are at risk of experiencing adverse drug events. We report a
case of skin lesion related to drugs and discuss consequences of polypharmacy in the elderly. An 85-yearold female took the following drugs for a long time: amlodipine, valsartan, hydrochlorothiazide, lysine
acetylsalicylate, sinvastatine, and trimetazidine. In June 2013, she presented thoracic pain and received
propranolol, tramadol, and paracetamol. One week later, she developed a diffuse skin lesion. In our
patient, drugs considered unnecessary were discontinued and corticosteroid was administered orally.
Careful monitoring helped improve the outcome. Corticoids were dangerous but necessary to correct the
consequence of iatrogeny.
Copyright 2014, Asia Pacic League of Clinical Gerontology & Geriatrics. Published by Elsevier Taiwan
LLC. All rights reserved.

Keywords:
drugedrug interactions
elderly
iatrogeny
polypharmacy
skin lesion

1. Introduction
The frequency of chronic illness and the expenditure for medications increase with older age.1 Polypharmacy and prescription
practices result in increased impairment in quality of life and in
drug-related morbidity and mortality.2 Nearly 50% of older adults
take one or more medications that are not medically necessary.3
Polypharmacy is variously dened as a large number of medications (> 5e10), use of more drugs than clinically indicated, or use of
inappropriate medications.4 A literature review found that polypharmacy continues to increase.5,6 Based on polypharmacy and
age-related pharmacokinetic and pharmacodynamic changes, the
risks of adverse drug reaction and adverse drug event are
increasing in elderly patients.7e10 In fact, it is estimated that elderly
people have four times greater odds of being hospitalized for
adverse drug reactions than those < 65 years of age (16.6% vs.
4.1%).11

* Corresponding author. Department of Medicine, El Idrissi Hospital, 112, Abou

Bakr Esseddik Avnue, Appartment number 8, Kenitra, Morocco.
E-mail address: bennirhita@yahoo.fr (R. Bennis Nechba).

This report describes a case of vesiculobullous disease in the

elderly associated with the administration of multiple drugs and,
using this example, discusses the consequences of polypharmacy in
the elderly.12e20
2. Case report
An 85-year-old female, having like antecedents of obesity, and
since 2002 had a cerebral ischemic stroke with physical disability,
an ischemic heart disease, and high blood pressure. Since
November 2012, she has taken a compact tablet of two compounds
at home (amlodipine and valsartan 5 mg/160 mg), hydrochlorothiazide 25 mg, lysine acetylsalicylate 160 mg, sinvastatine 20 mg,
and trimetazidine 35 mg In June 2013, she presented with thoracic
pain and also took propranolol 40 mg and a compact tablet of two
compoundsdtramadol with paracetamol 37.5 mg/325 mg. One
week later, she developed a diffuse vesicobullous disease associated with signicant pruritus, evolving in a context of conservation
of the general condition. Physical examination revealed large tense
blisters arising on normal skin. Several vesiculobullous lesions of
different age and were most common in the lower abdomen, arms,
and legs. The bullae were lled with clear uid, and some were
hemorrhagic. Examination of the healthy skin showed no peeling.

http://dx.doi.org/10.1016/j.jcgg.2014.06.002
2210-8335/Copyright 2014, Asia Pacic League of Clinical Gerontology & Geriatrics. Published by Elsevier Taiwan LLC. All rights reserved.

R. Bennis Nechba et al. / Journal of Clinical Gerontology & Geriatrics 6 (2015) 30e33

The mucous were respected (Figs. 1 and 2). Biological investigations

demonstrated the following: total leucocyte count, 10,800/mm3;
eosinophils, 108/mm3; hemoglobin, 10.9 g/dL; and platelets,
386,000/mm3. The C-reactive protein was 20 mg/L. Transaminase
Serum Glutamate Oxaloacetate Transaminase (SGOT) was 16 IU/L,
Serum Glutamate Pyruvate Transaminase (SGPT) 30 IU/L, urea
0.56 g/L, creatinine 13.23 mg/L, and blood glucose level 0.84 g/L.
The search of antibodies antibasement membrane by indirect
immunouorescence was positive. Skin biopsy was not performed.
The newly prescribed diuretic and drugs were discontinued. After
ruling out a possible infection, we prescribed to our patient oral
administration of 1 mg/kg of corticosteroid, local corticosteroid, an
antihistaminic drug, iron for a long time, and local fusidic acid for a
period of 15 days. The patient had a shower daily with an antiseptic.
She received a low-salt diet enriched with potassium, vitamins,
nutrients, and liquid contents. She has been assisted at home by her
daughter and an assistant nurse. Evolution of symptoms was
marked during the 1st month by relapses of lesions of different
ages. During the 2nd month, relapses became less frequent, and the
disease stabilized 3 months later. At the end of the 4th month and
after the healing of lesions, the dosage of orally administered
corticosteroid was reduced gradually. Unfortunately, the patient
developed recurrent blistering, and the full dose of 1 mg/kg of oral
corticosteroid was readministered. Each time we tried to decrease
the dose of corticosteroid to below 0.5 mg/kg, she presented new
vesicobullous lesions. Seven months later, the patient was stabilized by 0.5 mg/kg of oral corticosteroid (Figs. 3 and 4).
Electrolytes and blood glucose level remained normal. However,
the patient presented high blood pressure, acute bronchitis, and
epigastric pain. Her electrocardiogram had not changed; therefore,
she was again prescribed diuretic hydrochlorothiazide 25 mg,

31

Fig. 2. Vesicobullous disease. Large tense blisters arising on normal skin in the lower
abdomen of the patient. The bullae were hemorrhagic.

transdermal glyceryl trinitrate, preventive anticoagulants enoxaparin sodium 40 mg/0.4 mL, amoxicillin clavulanic acid 2 g, and
omeprazole 20 mg.
Sinvastatine 20 mg, trimetazidine 35 mg, antihistamic, and iron
were discontinued. Unfortunately, 2 days later, she presented the
same diffuse vesiculobullous disease again, so the full dose of 1 mg/
kg of oral corticosteroid was readministered and hydrochlorothiazide was discontinued. High blood pressure was treated using a
compact tablet of two compounds (amlodipine and valsartan
10 mg/160 mg), a long-term low-salt diet, and transdermal glyceryl
trinitrate for 1 month. Preventive anticoagulants, such as enoxaparin sodium 40 mg/0.4 mL, amoxicillin clavulanic acid 2 g, and
omeprazole 20 mg, were prescribed for a period of 10 days. After
suspending hydrochlorothiazide and increasing the dose of corticosteroid, the skin eruption improved gradually; hence, oral
administration of corticosteroid was reduced slowly. About 10
months later, our patient received only 20 mg of corticosteroid and
she has not presented any vesiculobullous disease since. Her blood
pressure is also stabilized.
3. Discussion

Fig. 1. Vesicobullous disease. Large tense blisters arising on normal skin in the right leg
of the patient. These lesions were of different ages. The bullae were lled with clear
uid; some were hemorrhagic.

Most elderly patients with comorbidities and polymedication

are excluded from clinical trials, and geriatrics was not considered a
priority during medical training.21 Now, geriatric pharmacotherapy
represents one of the biggest achievements of modern medical
interventions.22 However, geriatric pharmacotherapy is a complex
process that encompasses not only drug prescribing, but also ageappropriate drug development and manufacturing, appropriate
drug testing in clinical trials, rational and safe prescribing, and
reliable administration and assessment of drug effects, including
adherence measurement and age-appropriate outcome monitoring.22 To be able to improve outpatient health care management
for patients receiving multiple medications, the current status quo
of care, risk factors for decient treatment, and characteristics of
concerned patients must be investigated.21 Although drug prescribing is often benecial to patients, elderly patients are particularly exposed to the side effects of medications and their
consequences.1
Bullous-liked drug eruption is common.12,13,16,17,19,20 In our patient, the possibility of a drug-induced disease was considered
because she was taking nine different medications. The diagnosis of
a drug-induced disease was based on clinical, anamnesic, and
biological arguments. The pharmacovigilance center realized a
study of accountability, and the chronological analysis of events

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R. Bennis Nechba et al. / Journal of Clinical Gerontology & Geriatrics 6 (2015) 30e33

Fig. 3. Signicant improvement of vesicobullous disease in the right leg of the patient,
7 months later.

prompted us to suspect that tramadol paracetamol 37.5 mg/325 mg

as well as the newly prescribed propranolol 40 mg were probably
the precursors of the vesiculobullous skin lesion. For this reason,
these medications were discontinued. The hemodynamic status of
the patient also allowed us to discontinue hydrochlorothiazide
25 mg rst.
A causal relationship between drugs and skin eruption was not
clear at the beginning. However, when we observe the evolution of
the symptomatology, the most suspected drug was still the diuretic
hydrochlorothiazide (25 mg). In fact, there was a recurrence of skin
eruption after the drug was readministered, and skin eruption
improved after the drug was suspended. That might not happen
just by chance in real life, and based on this description we could
conclude that hydrochlorothiazide was related to the skin eruption.
The serological report could not replace the gold standard of
skin biopsy.23 Authors could not conclude that the vesiculobullous
lesion was bullous pemphigoid without biopsy results. There are
numerous causes for the occurrence of bullous skin lesions, such as
drug-related bullous disorder, toxic epidermal necrolysis, or SteveneJohnson syndrome.20 False positives might be a problem
related to the antibasement membrane antibody test.23
After the occurrence of vesiculobullous skin lesions and the
result of indirect immunouorescence, which showed that antibasement membrane antibodies were positive, our patient received

corticosteroid orally for a long period of time. This treatment was

necessary and imposed a rigorous surveillance because it has
various serious side effects that have widely been described in the
literature.12,13 The outcome of vesiculobullous skin lesion is
reserved (relapses, resistors, and dependence on corticosteroids).12,13 Mortality at 1 year is high, and the vital prognosis is
related mainly to side effects of the corticosteroid.12,13 Our patient
presented other drug events after she was prescribed oral administration of corticosteroid, such as high blood pressure, relapses,
dependence on corticosteroids, sepsis, and epigastric pain. She
required careful monitoring, and some drugs were discontinued
and others were prescribed to improve her outcome. Patients often
receive additional medications to treat side effects.4 Indications for
medication should be taken individually, in order to develop a
realistic riskebenet ratio, taking into consideration factors such as
quality of life and life expectancy.24
Most adverse drug reactions are preventable.21,25 Concerning
our patient, we noted that she received many medications, some of
which were unnecessary. We concluded that long-term use of a
compact tablet of two compounds (amlodipine and valsartan
10 mg/160 mg) was required to treat high blood pressure, lysine
acetylsalicylate 160 mg to prevent relapse of cerebral stroke and
ischemic heart disease, and corticosteroid to treat vesiculobullous
skin lesion. The patient was given a low-salt diet rich in potassium,
vitamins, nutrients, and liquid contents. All other drugs were discontinued. Evidence suggests that the patient would have died
soon had we stopped the necessary drugs, and her condition
improved after stopping unnecessary medications. Our patient
presented a signicant clinical benet after the reduction of prescribed drugs. In addition, physicians should pay close attention to
the medical history and current medication when adding a new
medication for elderly patients.7 In fact, corticosteroid was benecial and saved our patient's life. However, without any skin
eruption, corticosteroid would be harmful for a person with heart
disease (sodium retention, acute myocardial infarction with risk of
left ventricle rupture, etc.) or osteoporosis (bony fracture).12,13
In other words, with aging, people may have difculty following
a drug treatment for different reasons. Thus, they can put their
health at risk. Our patient suffered from physical disability. The help
of the family was important and improved patient adherence with
prescribed medications, a good medical and psychological assistance of the family was important and has considerably improved
the health status of the patient.
4. Conclusion
Health care delivery is not infallible. It is essential to optimize
drug prescription to the elderly. A combination of measures may be
necessary to improve the situation. More research is needed to
further delineate the consequences associated with drug use in
elderly patients.
Conicts of interest
Authors disclose that they have no potential conicts of interest.
Authors also ensure that they have no potential nancial and
nonnancial conicts of interest.
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Fig. 4. Improvement of the skin eruption in the lower abdomen of the patient, 7
months later.

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