Case Study 7 -- Photosensitive Rash And Resistant Hypertension

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.

Elizabeth Ho Moon Liang

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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

Elizabeth Ho Moon Liang

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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.

Elizabeth Ho Moon Liang

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Date 02 Feb 06 18 Feb 06

Consultation Notes Wants polyclinic for hypertension follow up care. BP: 160/100mmHg BP: 160/100mmHg (pre-meds)

10 Jul 06

BP: 160/100mmHg (post-meds)

22 Jul 06 02 Sep 06

BP: 130/70mmHg BP: 150/96mmHg Develop itchy rash for few months on and off. Rash and itch were worsened with enalapril. Also has mild cough. BP: 200/105mmHg No complains with Valsartan. BP: 190/100mmHg (Missed meds for 2 days) Tolerated Valsartan. BP: 160/100mmHg. (Post meds)

13 Sep 06 30 Sep 06 14 Oct 06 27 Oct 06

BP: 160/90mmHg Itch and cough, patient claims due to meds.

4 Nov 06

BP: 190/100mmHg (pre-meds) Not happy with meds. Still coughing

11 Nov 06

BP: 160/100mmHg Well on meds.

09 Dec 06

BP: 150/90mmHg Has pedal edema for 3 weeks on Amlodipine.

06 Jan 07

BP: 170/100mmHg

13 Jan 07

BP: 150/100mmHg (pre meds) Rashes started on upper limb.

27 Jan 07

BP: 160-120mmHg (post meds) Rashes spreading to photosensitive areas.

Medications Atenolol 50mg OM TCU: 3mths Atenolol 50mg OM TCU:3mths Atenolol 50mg OM. Add Enalapril 2.5mg OM. TCU: 2 weeks Same meds for 3mths. Stop Atenolol and Enalapril. Start Valsartan 40mg OM. TCU: 2 weeks Increase Valsartan 80mg OM. TCU: 2 weeks Increase Valsartan 120mg OM. TCU: 2 weeks Increase Valaartan 160mg OM. TCU: 2 weeks Start Valsartan. Start Adalat LA 30mg OM and HCTZ 12.5mg OM. TCU: 8 days. Off Adalat and HCTZ. Start Amlodipine 5mg OM and Losartan/HCTZ 50mg OM. TCU: 1 week Increase Amlodipine to 10mg OM. Losartan/HCTZ 50mg OM remain. TCU: 1 month. Stop Amlodipine. Increase Losartan/HCTZ 100mg OM. TCU: 1 month Start Atenolol 50mg OM. Losartan/ HCTZ 100mg OM remain. TCU: 1 month Off Atenolol. Losartan/ HCTZ 100mg OM remain. TCU: 2 weeks Losartan/ HCTZ 100mg OM remain. Add Nifedipine LA 60mg OM. Refer NSC. TCU: 1 week

Table 1: Summary of Polyclinic Consult

Elizabeth Ho Moon Liang

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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.

Elizabeth Ho Moon Liang

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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

Elizabeth Ho Moon Liang

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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.

Elizabeth Ho Moon Liang

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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.

Elizabeth Ho Moon Liang

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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. Elizabeth Ho Moon Liang

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