Iris Barrera, RN Has the Following Disclosures to Make

5/20/2020

Let’s Hash out the Drug Rash Part 2

Heartland National TB Center of Excellence Presented by Nurse Consultants: Iris Barrera, Catalina Navarro, Marybel Monreal

Webcast January 30, 2020

Iris Barrera, RN has the following disclosures to make:

•No conflict of interests •No relevant financial relationships with any commercial companies pertaining to this educational activity

1 5/20/2020

Catalina Navarro, RN, BSN has the following disclosures to make:

•No conflict of interests •No relevant financial relationships with any commercial companies pertaining to this educational activity

Marybel Monreal, BSN, RN has the following disclosures to make:

•No conflict of interests •No relevant financial relationships with any commercial companies pertaining to this educational activity

2 5/20/2020

Describe the characteristics of 3 Describe common types of skin lesions. Goal: Utilize current foundational knowledge to aid Utilize dermatological terminology to Utilize patients appropriately describe skin lesions. experiencing drug rash.

List List two rash identification resources.

But did you ask Public Health! 

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PHYSICAL ASSESSMENT RECAP: THE COMPONENTS GATHERING OF EPISODE SPECIFIC OF A RASH INFORMATION (HISTORY.) ASSESSMENT INCLUDE: OBTAINING LABORATORY AND OTHER DATA.

Physical Assessment

Observe the Location: Texture: Color: Red Purple patient’s reaction Arms Legs Torso Raised Flat Scaly Blanching for: Face Hands Feet Pustules Sloughing

Size: Distribution: Inspect Oral Warm to the touch Pinpoint Small Diffuse Localized Mucosa Large

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https://patient.info/doctor/common‐childhood‐rashes# Adapted by Dr Adrian M Bonsall, from the Pediatric Handbook 6th Ed. Royal Children's Hospital, Melbourne.

What other Questions to ask the Are you allergic to any Any other known medication or patient: medicines? allergies? Food? remedies have you been taking?

When did you first Have you been using a Any changes in your Is it: Itchy or painful? notice the reaction? different detergent? lifestyle?

Gathering episode specific information

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How long after your dose of Drug Rash medication did the rash • Typical symptoms include redness, bumps, blisters, hives, itching, and occur (minutes, hours, days) sometimes peeling, or pain.

• Every drug a person takes may have to be stopped to figure out which one is causing the rash. Has this happened before • Most drug rashes resolve once the with this medication drug is stopped, mild reactions may be treated with creams to decrease (increasing sensitivity) symptoms but serious reactions may require treatment with drugs such as epinephrine (given by injection), diphenhydramine, and/or a corticosteroid to prevent complications. Have you taken anything for the rash

Reference Materials

• Have a visual aid available to guide your assessment and documentation For image SEARCH KEYWORD: Rash terms with pictures • Dermatology Resource: UpToDate

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Common Lesion Types Macules: Flat, nonpalpable lesions usually < 10 mm in diameter. Macules represent a change in color and are not raised or depressed compared to the skin surface. A patch is a large macule. Examples include freckles, flat moles, and some allergic drug eruptions Macules

Common Lesion Types Papules Elevated lesions usually < 10 mm in diameter that can be felt or palpated. Examples include nevi, warts, insect bites, some lesions of acne.

Papules

7 5/20/2020

Common Lesion Types The term maculopapular is often loosely and improperly used to describe many red rashes; because this term is nonspecific and easily misused, it should be avoided. • Remember a macule is <10mm …the pictured reactions is much bigger. • Additional terms should be used

• Confluent: flowing or coming *Maculopapular together also : run together.

Common Lesion Types • Hives AKA Urticaria AKA Wheals: • Circumscribed, raised, erythematous plaques, often with central pallor. • Lesions may be round, oval, or serpiginous( wavy margin) in shape and vary in size from less than 10mm to several centimeters in diameter. They are intensely itchy • Individual lesions are transient, usually appearing and enlarging over the course of minutes to hours and then disappearing within 24 hours. Lesions may coalesce (come together) as they Hives aka Urticaria aka enlarge. Wheals

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Polling Question

What dermatological term best describes these non‐raised blanching erythematous skin lesions? A. Macules B. Papules C. Hives D. Maculopapular rash

Polling Question

What dermatological term best describes these non‐raised blanching erythematous skin lesions? A. Macules B. Papules C. Hives D. Maculopapular rash

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Macules are flat, nonpalpable lesions usually < 10 mm in diameter. Macules represent a change in color and are not raised or depressed compared to the skin surface.

Pictured is a Blanching erythematous macular rash in a patient with measles. Rationale

Polling Question

What dermatological term best describes these raised skin lesions? A. Macules B. Papules C. Hives D. Maculopapular rash

10 5/20/2020

Polling Question

What dermatological term best describes these raised skin lesions? A. Macules B. Papules C. Hives D. Maculopapular rash

Papules are elevated lesions usually < 10 mm in diameter that can be felt or palpated.

Pictured are multiple hyperpigmented papules present on the face of a patient with dermatosis papulosa nigra.

Rationale

11 5/20/2020

Polling Question

What dermatological term best describes these well circumscribed, erythematous plaques that are intensely itchy? A. Macules B. Papules C. Hives D. Maculopapular rash

Polling Question

What dermatological term best describes these well circumscribed, erythematous plaques that are intensely itchy? A. Macules B. Papules C. Hives D. Maculopapular rash

12 5/20/2020

Hives are circumscribed, raised, erythematous plaques, often associated with central pallor and are intensely itchy. Pictured is a urticarial drug eruption in a patient taking Moxifloxacin.

Rationale

Summary of Common Lesions portion

• A thorough physical assessment utilizing appropriate dermatological terms is critical to assisting physician recommendations and patient safety. • The term maculopapular is commonly misused and should be avoided. • Additional terms like confluent can better describe the reaction’s macular and/or papular presentation. • Remember: macules are flat discolorations and papules are elevated lesions; neither are larger than 10mm.

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Not all Rashes are Drug Rashes

“Nurse, I have a rash and I think it’s because of the medicine!”

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Objectives

1 Define atypical drug rashes

2 Define why some rashes are not drug rashes

3 Test your knowledge / self‐check

• Started anti TB therapy 3 weeks ago • Multiple erythematous papules primarily on wrist and fingers • Symptoms started 3 days ago • Itching worse at night

Is this a drug rash?

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• Started anti TB therapy 3 weeks ago • Multiple erythematous papules primarily on wrist and fingers • Symptoms started 3 days ago • Itching worse at night

Is this a drug rash? No

Scabies

• Infestation of the skin by the burrowing mite Sarcoptes scabie • Transmitted through direct and prolonged skin‐to‐skin contact (family members or sexual partners) • Manifests as intense eruption of pruritic papules with characteristic distribution • Common sites: fingers, wrists, axillae, areolae, and genetalia

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Classic Scabies Burrrows Crusted Scabies • Multiple small, erythematous • Burrows are characteristic • Poorly defined, erythematous papules, often excoriated but often not visible patches that quickly develop prominent thick scale crust • Severe pruritis, worse at night • Thin, gray, red, or brown lines • Seen more in older adults or • Diffuse distribution • 2 to 15 mm in diameter immunocompromised • Back relatively free of persons involvement • Develop on scalp, hands, and • Young children & infants: feet, although any skin area palms, soles, and fingers can be affected

If you suspect scabies

• Ask if itching is worse at night?

• Ask if itching is widespread o Usually not found on the head (unless infant or young child) • Are there other household members with similar symptoms?

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Miliaria / • Transient cutaneious disorder caused by occlusion or Heat Rash inflammation of the eccrine sweat duct • Sweating leads to miliaria: o Hot and humid environments, physical activity, febrile illness, Miliaria/ occlusion of the skin • Can affect infants, children, and adults Heat Rash o Neonates more susceptible • Miliaria has been reported in patients treated with medications that influence the sympathetic or cholinergic systems o α‐sympathomimetic drugs: clonidine, opiates, β‐blockers

Crystallina Rubra Profunda • Common in neonates, usually • Erythematous papules 2 to 4 mm • Erythematous skin‐colored, firm on head neck, and upper trunk • May be papulovesicular or pustular papules 1 to 4 mm • Superficial clear vesicles 1 to 2 • Itching or stinging worsened by • Blockage deep within sweat duct that mm in diameter sweating occurs after repeated episodes of rubra • No inflammation • Common in infants in skin folds of • Common in adults, usually on trunk but • In adults common on trunk neck, axilla, or groin can be on extremities • Asymptomatic • Anhidorosis, or absence of • Can cause anhidrosis sweating, can occur in affected area • Compensatory hyperhidrosis in nonaffected area –can lead to inefficient thermoregulation

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Chronic inflammatory skin disease

A mulitsystem inflammatory disorder associated with multiple comorbidities Psoriasis Affects males and females

Typical onset is in adulthood although it can occur at any age

Plaque Guttate Generalized pustular Erythrodermic •Erythematous plaque •Abrupt multiple small •Erythema, scaling, and •Uncommon •Sharply defined psoriatic papules and sheets of superficial •Acute or chronic plaque pustules margins < 1 to > 10 cm •Generalized erythema & •Thick silvery scale is •Usually < 1 cm •Causes: pregnancy, scaling on most of body common •Common on trunk and infection, & withdrawal of surface area oral glucocorticoids •Pruritis is common proximal extremities •High risk for infection & •Can have life threatening •May be asymptomatic electrolyte imbalance complications secondary to fluid loss Psoriasis

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Chiggers

Chiggers bites are caused by the larval form of trombiculid mites

Larvae are encountered in areas such as grasslands, forest, and lakes and streams

Mites can produce cutaneous lesions with allergic reactions

Also referred to as: harvest mites, harvest bugs, harvest lice, Mower’s mites

Chiggers: Cutaneous Manifestations

• Cutaneous inflammation • Intense pruritis • Grouped papules or papulovesicles • 1 to 2 mm in length • Bright red or red‐brown color • Flat or raised • Ankles and waistline often affected (where clothing contacts skin) • In boys a hypersensitivity response manifests with: penile swelling, pruritus, and dysuria

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Invasive Candida Infection:

• Invasive Candida infections are most often associated with candidemia, the presence of Candida species in the blood.

• Individuals at highest risk: Immunocompromised and patients in Intensive Care Units • Hematologic malignancies, transplant recipients, those receiving chemotherapy

• May have a fever to full‐blown sepsis

Candidemia: Cutaneous Manifestations

• Eye lesions, skin lesions, and less commonly, muscle abscesses • Skin lesions appear suddenly and painless as clusters of pustules with an erythematous base • Manifest on any area of the body • Size varies: • tiny pustules to nodular, up to several centimeters in diameter which may appear necrotic in the center. • In severely neutropenic patients, the lesions may be Large erythematous nodules Tiny pustular lesions macular rather than pustular. with central necrosis

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Bedbugs

• Obligate, blood feeding insects that inhabit human dwellings and may cause skin reactions • Present all around the world • Spread of infestation occurs through transportation of items harboring bedbugs • Can occur during travel, acquiring used furniture, or through direct movement in multifamily buildings or institutions • Do not live on humans • Live between cushions, cracks or crevices of mattresses • Attracted to host by warmth and generally feed at night while victim sleeps

Bedbugs: Cutaneous Manifestations

• Classic appearance is a 2 to 5 mm erythematous papule or wheal with a central hemorrhagic punctum • May appear as papular urticaria • A linear series of bites found upon awakening • Some persons only have asymptomatic purpuric macules • Bites usually resolve in one week

22 5/20/2020

Self Check

A 27 year old male patient who has been on RIPE for the past 8 weeks comes into the clinic complaining of some itching red spots that he noticed on his hands and legs yesterday morning when he woke up. He also states that the itching was so bad that he had trouble sleeping. On exam the nurse notices small erythematous papules in between his fingers and on his lower legs only. When questioned about any recent travel, the Patient states he has been home all weekend except when he left to pick up a new sofa his wife purchased at a yard sale. The patient denies any other symptoms.

Which of the following do you feel best desribes the cause of his cutaneous reaction?

a) Drug rash b) Psoriasis c) Scabies d) Chiggers bites e) None of the above

23 5/20/2020

Self Check

Which of the following do you feel best desribes the cause of his cutaneous reaction?

a) Drug rash b) Psoriasis c) Scabies d) Chiggers bites • Multiple small, erythematous papules e) None of the above • Severe pruritis, worse at night • Diffuse distribution • Back relatively free of involvement

NC2

Drug Rash with Systemic Symptoms

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NC2 Navarro, Catalina, 1/23/2020 5/20/2020

Immediate vs. Delayed Reactions

Drug-induced skin reactions can be classified according to timing:

• Immediate reactions: occur less than 1 hour of the last administered dose • Urticaria, angioedema, anaphylaxis*

• Delayed reactions: occur usually within 48 hrs. several days and frequently weeks to months after the start of administration

• Exanthematous eruptions •Systemic reactions: Steven Johnson Syndrome (SJS) and DRESS – begins 1‐12 weeks into continuous treatment

Drug Reaction with Eosinophilia and Systemic Symptoms DRESS . Skin eruption with systemic symptoms

. Fever, macular exanthem, erythematous facial swelling, malaise, lymphadenopathy

. Internal organ involvement (liver, kidney, heart, lung)

. Eosinophilia, atypical lymphocytosis (>70% of patients have eosinophilia)

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Eosinophils

Eosinophilia is an increase in number of eosinophils • CBC: Normal Value: Differential 1-6% • Absolute Eosinophils: 0.0 - 0.4 k/uL

Most often indicates: a parasitic infection, an allergic reaction or cancer

DRESS Epidemiology . Frequency varies depending on:  Type of drug and immune status of the patient  Incidence is estimated between 1/1,000-1/10,000 drug exposures . Fatality rate may be up to 10% . Signs and symptoms typically begin 1 to 12 weeks after start of the medication or after increasing the dose . Symptoms may continue despite the discontinuation of the culprit drug . Frequently associated with the reactivation of herpes virus infection

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Medications Implicated in DRESS:

Anti-TB Drugs • Anticonvulsants * • Isoniazid • Streptomycin • Antibiotics • Rifampin • NSAIDs • Ofloxacin • Anti-retroviral Drug • Ethambutol • Cycloserine • Allopurinol *

Case Study ‐ Background

• 21 y/o healthy female

• Prior treatment for LTBI with INH

•NKA

• In Jan 2014 Dx’d with cavitary pulmonary TB by the local Health Department

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Course of Treatment

RIPE started

LEVO Amikacin added

2/5/14 RIPE started Clinical improvement 4/23/14 (9 weeks after TB Nausea after meds for few Mild nausea was reported treatment initiation) hours, normal LFT’s LFT’s repeatedly normal INH d/c Low level INH resistant Addition: Levo and Amikacin

DRESS CASE –12 weeks after TB RX

• 5/14/14: Treatment regimen RIF/EMB/PZA/Levo and Amikacin o Headache, nausea, fever, chills, malaise o Normal exam and LFT

• 5/15/14: ED visit for fever, diarrhea • Normal LFT, diagnosis of UTI, infectious diarrhea • Added Cipro/Tylenol

• 5/20/14: worsening symptoms and RASH o Seen by healthcare provider ED TB Meds stopped Fever o Malaise visit • 5/22/14: Local Hospital admission RASH Hospital RASH o Labs: AST: 318, ALT: 443, AP: 263, Tbili:2.3 Admit o Exam: mucositis, ulcers to palate tongue, buccal mucosa o Widespread macular and papular eruption RASH

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DRESS CASE – Hospitalization #1

Extensive mucositis, ulcers to palate, tongue, buccal mucosa, widespread macular and papular eruption TB meds held 5/20, start IV steroids

DRESS CASE – Hospitalization #1 Fever, progressive cutaneous eruption Widespread confluent macular and papular eruption

Hospital Day 3

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Hospital Day 5

Hospital Day 5 Although the medications were stopped and the patient’s symptoms were gradually improving, the LFT’s began to rise

Labs – Hospitalization #1

Date H/H AST ALT T Bili Alk Pho Platelets Eosinoph Comments 5/24 12/38 437 558 2.9 319 176 Severe rash 5/25 12.4/37.2 438 654 2.1 303 188 Severe rash mucositis 5/26 12.8/38.7 352 604 1.7 270 187 Mucositis facial edema 5/27 12/36 248 462 2.2 241 199 5/30 10.6 1313 96 253 126 RASH improved, 6/1 5715 3142 2.6 LFT’s peak /fever resolved 6/2 11.2/34 3463 2829 3.4 232 88 Liver transplant was discussed 6/3 11/33.5 1114 1880 2.8 79 6/4 11.3/34 535 1566 1.9 259 95 6/9 321 79 1.9 128 Discharged from local hospital

Remember: TB meds have been on hold since 5/20/14

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Liver Disease Evaluation Workup for other organic causes of liver failure was negative – HIV and hepatitis panel

– CT of abdomen

– HIDA scan (hepatobiliary scan)

– RUQUS (RUQ u/s)

– Rickettsia screen

– Monospot test

End of Hospital Course

• Rash improved in one week • Mucositis resolved • LFT’s normalized • Fever resolved by June 1st • Discharged from local hospital on 6/9/14

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DRESS CASE – Outpatient Care

• 6/23/14: (One month after stopping TB mds) Re‐challenge with RIF 600 mg o Questionable slight dizziness, mild nausea LFT’s resolved quickly Peak

Discharged

• 6/24/14: Received RIF 600 mg • Later that day abdominal pain, nausea, Re‐ fever, diffuse rash, and appeared jaundice challen RIF Re ge 600 mg admit

RIF was held and patient was readmitted to the local hospital

Labs – Hospitalization # 2

• Suspected cholecystic jaundice, however LFT’s were WNL • Eosinophilia was noted

Date AST ALT T Bili Alk Pho Eosinophils Comments 6/25 60 59 10.4 223 17% 6/27 16 7 0.9 7/3 14 21 1.8 Discharged off TB meds

• Due to a spike in TBili after 2 doses of RIF the patient required specialized TB care and was transferred

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Admission to TCID Texas Center for Infectious Disease

San Antonio, Texas

DRESS CASE – Hospitalization #3 (TCID) 7/7/14 • Labs on admission: Within normal limits • Re-challenge with one TB medication every 3 days with close monitoring – Moxifloxacin, EMB, linezolid and amikacin – Tolerated these medications well • 12 days after TB medications were restarted Eosinophilia worsened peaked at 22% • Clinically stable, no rash, no GI symptoms • Labs were stable during hospitalization

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TCID TB Treatment Plan • MDR-TB regimen due to: – Rifamycin intolerant – Low level INH resistant

New plan: • Pt was given credit for treatment received prior to admission • Extended treatment for 12 months

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DRESS CASE –Hospital Course at TCID • Patient improved clinically, radiographically and bacteriologically with TB therapy • Patient was discharged from TCID 3/4/2015

• Patient continued TB treatment by DOT as outpatient

DRESS was highly considered in the differential diagnoses

How could you confirm or exclude DRESS?

DRESS Diagnosis No criterion standard for diagnosis of DRESS

European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) developed a scoring system based on:

 Extent of skin involvement

 Organ involvement

 Clinical course

 Scoring cut-off points: < 2 no DRESS, 2-3 Possible, 4-5 Probable, ≥6 Definite

RegiSCAR: http://tools.farmacologiaclinica.info/index.php?sid=10001 – Tools to help score for DRESS

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Approach to the Patient with Suspected DRESS • Complete skin exam • Order CBC, LFTs, BUN, creatinine • Identify the offending medication • Identify if the patient is on medications known to precipitate DRESS: i.e., anticonvulsants, allopurinol, antibiotics, NSAID’s, and ART • Review clinical history • STOP (or substitute) all suspect medications • Seek hospitalization in addition to expert consultation

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DRESS: Patient Education

• Most patients with DRESS recover completely in weeks to months after drug withdrawal • Education about the need for a strict avoidance of the offending drug as well as cross-reacting drugs • Autoimmune diseases have been reported in some patients months or years after the resolution of the drug reaction – Graves disease, diabetes mellitus type 1, and autoimmune hemolytic anemia

Take Home Points

. A detailed medication history

. Documentation of all reactions with detailed description in patients chart

. When a patient presents with a combination of rash and facial swelling order CBC and LFT’s

. Signs and symptoms of DRESS may persist and recur for many weeks even after cessation of the offending medication

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NC2 Acknowledgement

• Dr. Barbara Seaworth • Dr. Adriana Vasquez • Dr Annie Kizilbash

Texas Center for Infectious Diseases ‐ TCID

References

• Drug rash with Eosinophilia and systemic symptoms syndrome induced by clelcoxib and Anti‐TB Drugs. Joo Ho Lee, et al. J Korean Med Sci 2008. DOI: 10.3346/jkms.2008.23.3.521

• Uptodate.com/contents/drug‐reaction‐with‐eosinophilia‐and‐systemic‐symptoms‐dress

• Drug Reaction with Eosinophilia and Systemic Symptoms: an update on pathogenesis. Camous, et al. Current Opinion in Immunology 2012,24:730‐735

• James, William D, Dirk M. Elston, Timothy G. Berger, and George C. Andrews. Andrews' Diseases of the Skin: Clinical Dermatology. London: Saunders/ Elsevier, 2011. Print.

• Comparison of Diagnostic Criteria and Determination of Prognostic Factors for Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome. Dong‐Hyun Kim, Young‐Il Koh. Allergy Asthma Immunol Res. 2014 May; 6(3): 216–221. Published online 2014 February 6. doi: 10.4168/aair.2014.6.3.216. PMCID: PMC4021239

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NC2 Navarro, Catalina, 1/23/2020 5/20/2020