CASE STUDY 7 Hypertension Drugs Allergy

Dated: 25 June 2007

Patient’s Name: Cheng H.Y. NIRC: S00*****D

TABLE OF CONTENTS
Page
1. Patient Profile 2

2. Health Assessment 2

3. Physical Examination 5

4. Diagnosis 5

5. Management 6

6. Evaluation 9
7. APN reflections and learning points 10

A 54-year old lady with hypertension presented with photosensitive rashes on 3 February 2007.
This case study will be focusing on the 1) approach to photosensitive rash and 2) management of
persisting hypertension.

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PATIENT PROFILE
Ms Catherine Cheng (S0054278D), a 54-year old lady, has hypertension for about 3 years. She
was also diagnosed having proteinuria and renal impairment with a CCT of 46ml per minute. She
was attended on the 3 February 2007 for her hypertension control and rashes. This case study
will be focusing on the 1) approach to photosensitive rash and 2) management of persisting
hypertension.

HEALTH HISTORY
Chief Complains: Ms Catherine came for a follow-up appointment for hypertension and rashes
review. She complained that her left leg swells usually at about 4pm after she took the Nifdepine
LA 60mg in the morning. Her skin rashes are still persisting but have resolved slightly. They are
still very itchy but there are no new areas of rashes appearing.

Clinical History: Ms Catherine has been following up in Hougang polyclinic for high blood
pressure control. From 2 Feb 2006 to 3 Feb 2007, her clinic blood pressure readings range from
150/90mmHg to 200/105mmHg. She had tried (1) Beta Blockers: Atenolol, (2) ACE-inhibitors:
Enalapril and Valsartan, (3) Calcium channel blockers: Adalat LA and Amoldipine and (4)
Diuretics: Hydrocholrothiazide and (5) Combination drugs: Losartan/ Hydrochlorthiazide
(Hyzaar amd Hyzaar Forte). During the consult on 3 February, her blood pressure was
160/108mmHg and 170/110mmHg with antihypertensive medications. She denies having
headache, nausea, vision disturbances and neurological symptoms during consult.

It was noted that papular rashes appeared on Catherine’s upper limbs on 06 January 2007. The
rashes were papular and pruritic in nature. The distribution of rashes is in photosensitive areas,
predominantly over the neck, upper limbs, face, bridge of nose and feet. The medications she
was taking every morning once a day during that period of time were 1) Losartan/
Hydrochlorthiazide 100mg/ 25mg 2) Atenolol 50mg 3) Calcium and Vitamin D 1 tablet and 4)
Glucosamine 1500mg. Losartan/ Hydrochlorthizaide combination drug was prescribed to
Catherine since November 2006 which she had tolerated the medications with no side effects
reported. She was also prescribed Atenolol from 2004 to 2006 with no allergy reported. She was
only restarted back on Atenolol with Losartan/ Hydrochlorthiazide combination on the previous
consult prior to developing rashes. She claimed there was no changes in the topical agents that

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she was using. She was referred to the National Skin Center with an appointment date on the 9th
February.

She reported that the rashes were better during this consult. However, she is experiencing
swelling of the feet usually around 4pm after taking Nifedipine LA 60mg in the morning. The
swelling resolves usually the next morning. There is no report of shortness of breath or exertional
dyspnea.

Catherine has no history of chronic skin problems. There is also no other significant medical
history of note. She works as a factory operator dealing with packaging of batteries for more than
1 year. There is no exposure of batteries contents during the course of work. There are no
reported joint pains. Review of other systems is negative.

Current Medications:
1) Losartan/ Hydrochlorthiazaide 100mg every morning
2) Nifedipine LA 60mg every morning
3) Hydroxyzine 10mg morning and afternoon, 25mg in the evening
4) Betamethasone Valerate 0.025% cream

Drug Allergy:
Nil reported. However, from her medical notes, it has been noted that Catherine seems to
develop side effects to the following medications.
1) Enlapril – cough
2) Valsartan – headache and cough
3) Amolodipine – pedal edema
She exhibited rashes from enalapril with mild cough and pedal edema from amlodipine. She also
complained having cough and headache with Valsartan. On one of the consults that she
verbalized unhappiness with Adalat LA and hydrocholrothiazide regimen. See Table 1 for the
summary of polyclinic consults.

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 Date Consultation Notes Medications
02 Feb 06 Wants polyclinic for hypertension follow up care. Atenolol 50mg OM TCU:
BP: 160/100mmHg 3mths
18 Feb 06 BP: 160/100mmHg (pre-meds) Atenolol 50mg OM
TCU:3mths
10 Jul 06 BP: 160/100mmHg (post-meds) Atenolol 50mg OM. Add
Enalapril 2.5mg OM.
TCU: 2 weeks
22 Jul 06 BP: 130/70mmHg Same meds for 3mths.
02 Sep 06 BP: 150/96mmHg Stop Atenolol and Enalapril.
Develop itchy rash for few months on and off. Start Valsartan 40mg OM.
Rash and itch were worsened with enalapril. TCU: 2 weeks
Also has mild cough.
13 Sep 06 BP: 200/105mmHg Increase Valsartan 80mg
No complains with Valsartan. OM. TCU: 2 weeks
30 Sep 06 BP: 190/100mmHg (Missed meds for 2 days) Increase Valsartan 120mg
Tolerated Valsartan. OM. TCU: 2 weeks
14 Oct 06 BP: 160/100mmHg. (Post meds) Increase Valaartan 160mg
OM.
TCU: 2 weeks
27 Oct 06 BP: 160/90mmHg Start Valsartan.
Itch and cough, patient claims due to meds. Start Adalat LA 30mg OM
and HCTZ 12.5mg OM.
TCU: 8 days.
4 Nov 06 BP: 190/100mmHg (pre-meds) Off Adalat and HCTZ.
Not happy with meds. Still coughing Start Amlodipine 5mg OM
and Losartan/HCTZ 50mg
OM.
TCU: 1 week
11 Nov 06 BP: 160/100mmHg Increase Amlodipine to
Well on meds. 10mg OM.
Losartan/HCTZ 50mg OM
remain.
TCU: 1 month.
09 Dec 06 BP: 150/90mmHg Stop Amlodipine.
Has pedal edema for 3 weeks on Amlodipine. Increase Losartan/HCTZ
100mg OM.
TCU: 1 month
06 Jan 07 BP: 170/100mmHg Start Atenolol 50mg OM.
Losartan/ HCTZ 100mg OM
remain.
TCU: 1 month
13 Jan 07 BP: 150/100mmHg (pre meds) Off Atenolol.
Rashes started on upper limb. Losartan/ HCTZ 100mg OM
remain.
TCU: 2 weeks
27 Jan 07 BP: 160-120mmHg (post meds) Losartan/ HCTZ 100mg OM
Rashes spreading to photosensitive areas. remain.
Add Nifedipine LA 60mg
OM.
Refer NSC.
TCU: 1 week
Table 1: Summary of Polyclinic Consult

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PHYSICAL EXAMINATION
General appearance – Type: Urticaria Erythematous Papules, Shape: round and dome shaped,
Arrangement: Diffuse involvement, Distribution: Sun-exposed region.
Temperature – Afebrile.
Nails –No nails changes. No pallor and clubbing seen.
Eyes – No conjunctivae pallor noted. No papilloedema noted.
Tongue – Moist. Not cyanosis.
a) CVS examination
Pulse – 90 beats per minute. Regular in nature.
Blood Pressure – 160/ 108mmHg and 170/ 110mmHg (post-meds)
Heart – Apex beat palpable between 4th and 5th intercostals space. No thrills and heave felt. S1
and S2 sounds heard. No murmurs detected. Jugular venous pressure not raised. No pedal edema.
b) Lungs examination
Lungs – Respiration rate 12 breaths per minute. Trachea is not deviated. Chest expansion is
bilaterally equal. Vesicular breath sounds hear. No wheezes or rhonchi are detected upon
auscultation.
c) Abdomen examination
Abodmen is not distended. Soft and non-tender. There is no organmegaly. Kidneys are not
ballotable. No renal bruits are detected.
d) Neurological examination
No abnormalities noted.

DIAGNOSES
Principal Diagnosis: Persistent hypertension
Probable Diagnosis: Photosensitivity Dermatitis secondary to drug allergy.
Differentials: Contact Dermatitis, Rosacea, Lupus Erythamous and Dermatomyositis
The urgency to rule out drug allergy is important in Ms Catherine’s case as drug allergy can lead
to other severe complications e.g. anaphylactic shock. In addition, her hypertension management
needs to be optimized. On 2 occasions in September and October 2006, she complained about
itch and rash. The clinical symptoms seem to coincide with addition of ACE and ARBs to the
treatment plan. However, there is a possibility that recurrent episodes of itch and rash can be
triggered from of an unknown primary irritant resulting in contact dermatitis.

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MANAGEMENT
Approach to Photosensitive Rashes. Identification of light playing a role in the development of
rash is essential before the approach to photosensitive rash can be used. This involves
recognizing the distribution of the rashes mainly noted on forehead, tip of nose, upper cheeks, V
of chest, outer arms and dorsa of hands. Shaded areas like trunk, axilla regions and flexures tend
to be spared. According to Kwok (2002), photodermatoses can be divided into 4 major groups
and the morphology of rash narrows the differential diagnoses (See Table 2 and 3).

Retrospectively reflecting, in Ms Catherine’s case, which she presented with erythema, urticaria
and papules, drug-induced photosensitivity rash as the probable and the list of differentials seem
appropriate.
Drug photosensitivity
Systemic phototoxicity
Systemic photoallergy
Phototoxic contact
dermatitis Photoallergic
contact dermatitis

Photo-aggravated dermatoses
Endogenous eczema
Collagen vascular disease

Idiopathic acquired photodermatoses

Polymorphic light eruption
Actinic prurigo
Hydroa vacciniforme
Solar urticaria
Chronic actinic dermatitis
Genodermatoses & Metabolic disorders
Porphyrias
Genodermatoses
o Xeroderma pigmentosum
o Cockayne's syndrome
o Bloom's syndrome

Nutrional deficiencies
o Pellagra
o Hartnup disease

Table 2: 4 Major Classification of Photodermatoses

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 Morphology Differential Diagnoses
Erythema Sunburn
Drug phototoxicity
Lupus erythematosus
Dermatomyositis
Urticaria Solar urticaria
Erythropoietic protoporphyria
Porphyria cutanea tarda
Drug induced urticaria
Oedema Solar urticaria
Polymorphic light eruption
Lupus erythematosus
Papules Polymorphic light eruption
Systemic lupus erythematosus
Actinic prurigo
Blisters Polymorphic light eruption
Hydroa vacciniforme
Porphyria cutanea tarda
Drug phototoxicity
Phototoxic contact dermatitis
Eczema Chronic actinic dermatitis
Photoaggravated eczema
Lupus erythematosus
Dermatomyositis drug photoallergy
Photoallergic contact dermatitis
Scars Discoid lupus erythematosus
Actinic prurigo
Hydroa vacciniforme
Porphyria cutanea tarda
Erythropoietic protoporphyria
No rash Polymorphic light eruption
Sine eruptione
Erythropoietic protoporphyria
Drug induced phototoxicity
Table 3: Morphological Clues in Photodermatoses

Dermatomyositis is a rare idiopathic disorder that includes characteristics skin manifestation and
inflammatory myopathy. These patients usually present with other symptoms like proximal
muscle weaknes, dysphonia or disphagia. Other possible symptoms include respiratory muscle
weakness, visual changes and abdominal pain. Patients diagnosed with dermatomyositis have a
6.5-fold increased risk of malignancy. This risk is further increased if the age of diagnosis is

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after 45 years of age. Ovarian and gastric cancer, and lymphoma are highly associated with
dermatomyositis. A complete initial gynecologic evaluation with repeated gynecology screening
is thus necessary for a woman with dermatomyositis (Koler and Montemarano, 2001).

Thus, a presentation of photosensitive rash in the primary care setting requires health history
taking and physical examination covering aspects of malignancy, joints and musculoskeletal
involvement. Family history of malignancy and collagen vascular disorders like SLE might also
give an estimate picture of the risk profile.

Hypertension Drug and Skin Rash. Thiazides, captopril and frusemide are noted to commonly
cause serious reactions. Certain anti-hypertensive drugs are associated with specific morphologic
patterns. Other anti-hypertensive drugs that are noted to cause skin rashes include: ACE
inhibitors (particularly Enalapril), calcium channel blockers (particularly Diltazem, amlodipine
and nifedipine) and beta blockers (particularly Propanolol). Hydralazine is note to be commonly
associated with drug-induced SLE (Blume, 2007).

Treatment. Besides determining the cause of the photosensitive rashes. Stopping the suspicious
causative agent to the development or aggravation of the rashes is important. From the medical
history notes, it has been noted that the physicians had immediately stopped the agent that they
thought has caused the eruptions. This conclusion is usually derived from the health history and
analyzing the onset of rashes in respect to the timing that the medication has been started.

Drug-induced Rash Medications. Most of drug eruptions treatment is mainly supportive in

nature. Antihistamines can help block the release of histamine and provide symptomatic relief of
the pruritus. Topical corticosteroid agents can also provide symptomatic relief of pruritus.
Hydroxyzine 10mg for morning, afternoon and 25mg for night and Bethamethasone valerate
0.025% cream were prescribed in the previoius consult.

Hypertension Management. Excluding complications and determining causes for persistent high
blood pressure is necessary approach to patient with very high blood pressure reading. An APN
should refer the patients who fall into this category and manage under the supervision of the
physician.

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In Ms Catherine’s case, home monitoring was strongly encouraged. The comparison of the home
monitoring versus the clinical reading will be useful, in view that a proportion of the patients
have white coat hypertension. Her last creatinine level was 96umol/L on 06 January 2007, which
had dropped from 109umol/L in October 2006. The serum potassium was within normal range
and there was no evidence of fluid congestion. As pedal edema was present only after the
introduction of Nifedipine LA 60mg in the prior visit, the drug was taken of the prescription list.
Hydralazine 25mg three times a day was added to the hypertension treatment regimen.

The following medications were prescribed to Ms Catherine on 3 February 2007:

1) Continue Hydroxyzine 10mg morning and afternoon, 25mg in the evening
2) Continue Betamethasone Valerate 0.025% cream
3) Continue Losartan/ Hydrochlorthiazaide 100mg every morning
4) Add Hydralazine 25mg three times a day

EVALUATION
Follow up visits for Ms Catherine was scheduled to return 2 weeks later in view of her high
blood pressure reading and her skin manifestations. The next follow up visit will include
assessing the resolution of the skin rashes and high blood pressure management. From the
National Skin Centre report, hydrochlorothiazide seems to be the most probable agent to cause
Ms Catherine’s photosensitive rash. Most literature stated that the onset of reaction is rarely less
than 1 week or more than 1 month (Riedl and Casillas, 2003). However, Catherine had started on
thiazide since 27 October 2006. The time period between the introduction of drug and the onset
of reaction is about 3 months. The polyclinic physicians knew this information in the subsequent
visit.

Assessing complications of high blood pressure, like renal and cardiac problems, stroke and
papilloedema is also part of the care. The decision to send Ms Catherine to the specialist, in view
of her present proteinuria and mild renal impairment status, should be considered in subsequent
visits if the blood pressure is still not controlled despite treatment. Signs of fluid overload, e.g.
swelling ankles, exertional dyspnea etc. will increase the suspicion of renal deterioration and
require urgent referral to the specialist.

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APN RFLECTION AND LEARNING POINTS
Hypertension is a very common chronic disease problem that can be seen in the polyclinic
setting. It is interesting that through the case study write up, I get to learn more about
hypertension drugs that will cause photosensitive rashes and other dermatological presentations
that some might bring. It is also important to note for an APN that the approach to photosensitive
rash can at times go beyond just dermatological origin and could be malignancy related.

REFERENCES
Blume. J.E. Drug eruptions. Retrieved on 10 June 2007 from http://www.
emedicine.com/derm/topic104.htm

Koler. R.A. and Montemarano, A. (2001). Dermatomyositis. American Family Physician, 64(9),
p. 1565-1572.

Kwok, C. (2000). Evaluation of a photosensitive rash. National Skin Centre Bulletin for Medical
Practitioners, 11(1). Retrieved on 14 June 2007 from
http://www.nsc.gov.sg/cgi-bin/WB_ContentGen.pl?id=283&gid=54

Riedl, M.A. and Casillas, A.M. (2003). Adverse drug reactions: types and treatment options.
American Family Physician, 68(9), p. 1781-1790.

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