Cutaneous ID for the office part 3:Emerging infectious trends and those

that may require hospitalization

Harper N. Price, MD, FAAD, FAAPDivision Chief, Fellowship Director

Division of Dermatology

Objectives

• Identify more serious and emerging infectious related dermatoses that may present acutely to the office or more urgent setting.

• Recognize when emergency care and hospitalization is indicated.

• Review work-up, complication and treatment plan for these dermatoses.

Topics to Cover

• MIMR and related disorders• Strep infections• Eczema herpeticum• HFMD• Staph scalded skin• COVID?

Mycoplasma pneumoniae associated cutaneous eruptions• Morphologically diverse group• Mucositis alone• Mucositis with sparse cutaneous involvement• Mucositis with moderate skin involvement

• Distinct from erythema multiforme, SJS, TEN• Only mucositis: “incomplete SJS”, “Fuchs syndrome”, and

“Mycoplasma pneumoniae-associated mucositis”

Canavan T. N. et al. J Am Acad Dermatol 2014^Ramien. CED 2020

^

Mycoplasma induced rash and mucositis:Introducing “MIRM” ( “murms”)• Mucocutaneous reaction to Mycoplasma pneumoniae infection

• Used to be considered SJS variant due to MP infection

• Younger patients (mean=12), male predominance

• Universal prodromal symptoms for ~ 1 week

• Ocular involvement (82%)

• Urogenital lesions (63%)

Canavan T. N. et al. J Am Acad Dermatol 2014c

Mycoplasma induced rash and mucositis: clinical• Polymorphic skin lesions• Vesiculobullous (majority)• Targetoid• Papules/macules

• BSA is often sparse (47%) or severe mucositis alone (34%)

• Mucositis in majority• Isolated erosions• Ulcers• Vesiculobullous lesions• Severe involvement of buccal mucosa and denudation

Canavan T. N. et al. J Am Acad Dermatol 2014

MIRM suggested work-up

• ESR, CRP, CBC, CMP• MP—PCR and serology • Chest radiograph• NP or OP swab for MP and Chlamydophilia pneumoniae, respiratory

viruses, HSV• Skin biopsy generally not useful

Ramien. CED 2020

MIRM: diagnosis and management • Mucosal lesions >> Skin lesions (EM = skin > mucosal)

• Treatment: • If Mycoplasma positive, azithromycin • Supportive care à Vaseline, Mupirocin, +/- Triamcinolone• Nutrition for TPN vs. NG tube • Pain management

• Other consultants:• Ophthalmology, close follow-up• Urology (if dysuria or significant genital lesions)

• MIMR is not SJS/TEN or EM• MIMR does not progress to SJS/TEN (not drug induced)

Canavan T. N. et al. J Am Acad Dermatol 2014

Canavan T. N. et al. J Am Acad Dermatol 2014

Treatment of MIRM

• Review of cases showed diverse treatments (next slide)• Antibiotics to treat Mycoplasma • IVIG• Systemic corticosteroids • Supportive care• TNF blockers• NEWà Cyclosporine

• Ophthalmology, urology/GYN, nutrition and dermatology consults

• Supportive care is primary, IVIG in mucositis only cases failing supportive care

Canavan T. N. et al. J Am Acad Dermatol 2014Ramien. CED 2020

Ramien. CED 2020

Prognosis and sequela of MIRM

• Majority of patients have full recovery, mortality very low

• Sequelae:• Respiratory and oral/esophageal involvement, higher acuity• Skin: post-inflammatory changes• Ocular: conjunctival shrinkage, corneal ulcerations, dry eyes, blindness, ocular

synechiae, loss of lashes• Oral or genital synechiae

How often does MIRM recur?

• Reports remain sparse

• Recurrence rates* to date: 8%, 38%• Months to years• Seasonality (Oct to Feb) • ED, outpatient clinic and inpatient

• May be less severe than initial outbreak

*Meyer Sauteur et al. JAAD. 2020*Liakos et al. Pediatr Dermatol. 2020

(my) Lessons learned from MIRMs cases

• Don’t trust respiratory PCR, use serum PCR or Ab panel for Mycoplasma

• Often 2-3 mucosal sites, make sure you check GU areas

• Avoid NSAIDS if severe oropharyngeal involvement

• Get nutrition involved early, may need TPN

• Prolonged hospital course due to mucositis, pain

• Role of early treatment with systemic steroids?

Reactive Infectious Mucocutaneous Eruptionor “RIME"

• Broader spectrum of pathogens causing mucocutaneous disease• Chlamydophilia pneumonia, influenza B, human

metapneumovirus, human parainfluenzavirus, rhinovirus, enterovirus

• MIRM may be best under umbrella term of “RIME”

Pediatric erythema multiforme: a review

• Considered uncommon to rare• Mean age 5.6 y (neonate to 17 yo)*

• Acute, inflammatory, mucocutaneous condition

• Triggered by infectious agents• HSV, Mycoplasma, Cocci (AZ)

• EBV, CMV, VZV, Strep, adenovirus, chlamydia pneumonia, orf

• Less common triggers: drugs, vaccines (infant)

• THINK: INFECTION, INFECTION & INFECTION!

Zoghaib et al. JAAD. 2019*

Pediatric EM: clinical• Clinical diagnosis, biopsy often not needed

• EM presentation: Abrupt onset of targets• Favors acral sites, wrists/palms/soles• Skin > Mucosal involvement• Major (> 2 mucosal sites)and minor (1 site)

• Classic, 3 –ringed target lesions; static

EM does not = SJS/TENEM does not progress to SJS/TEN

Lesions are static

Erythema multiforme: management

• Laboratory workup • Mycoplasma NP swab, PCR or Abs• Direct PCR for HSV or serum PCR, Abs• Other viral studies based on symptoms• CBC, electrolytes

• Treatments vary, often supportive care• Systemic steroids (EM is very steroid responsive!)• Antivirals or antibiotics• Magic mouthwash• Topical steroids and anti-histamines (pruritus)

Erythema multiforme: management contin’

• Uncomplicated cases can often be managed outpatient• Usually with limited mucosal involvement and systemic symptoms• Council on symptoms and signs for urgent return

• Reasons for ED visits, admission• More mucosal involvement (decreased PO, pain)• Infectious etiology with systemic symptoms• Unclear diagnosis• Failed outpatient management

• Recurrent EM (~14%)*, often to HSV

Zoghaib et al. JAAD. 2019*

Pediatric skin and soft tissue infections

• About 25% of pediatric encounters, often ED or clinic

• Wide spectrum, necessitating accurate diagnosis and work-up

• Cultures are often not obtained, before empiric antibiotics

• Staphylococcus aureus and Streptococcus pyogenes are most common causes of community-onset SSTIs• Cutaneous infections with nephritogenic strains of S pyogenes are major

antecedent of poststreptoccal glomerulonephritis

Staph scalded skin syndrome (SSSS): facts

• Overall prevalence 0.09 to 0.56 per million• Mortality approx. 0.3% in pediatrics*, 2019 (4% reported prior)

• Usually in children younger than 5, between 2-3 years of age

• African-American children less susceptible than Caucasian

• More common during the summer and autumn months

• Incubation from 1 to 10 days after, average 5

*Arnold et al. JAAD .2018.

Staph scalded skin syndrome (SSSS)

• Superficial blistering skin condition

• Epidermolytic (exfoliative) skin toxins A and B produced by Staphlococcusspecies

• Neonates & young children most vulnerable• Lack of antitoxin antibodies• Decreased renal excretion of toxin, immature renal function

• Older children and adults• Chronic illness, immunodeficiency, renal disease• Overwhelming staphylococcal infections (excessive toxin)

Staph scalded skin syndrome (SSSS): clinical • Localized infection: conjunctivae, nares, perioral region, perineum,

umbilicus or non-skin source (e.g., otitis media, pharyngitis)

• Neonatal source: circumcision site, omphalitis, diaper areas

• Fever, malaise, lethargy, irritability, poor feeding, painful skin

• Erythemaà superficial fragile blisters à erosions/desquamation• Accentuated in creases

Radial fissures around mouth“Sad facies”

Around openings and creases

No mucosal extension

SSSS workup & treatment

• Culture skin sites 1st (eyes, nose, groin, umbilicus, axilla)• Look for systemic source, occasional strep scalded skin• Sensitivities (MSSA vs MRSA)

• Blood cultures (in older population?)

• Fluid and nutritional support, avoid NSAIDs

• Risk for secondary infection and sepsis• Petrolatum to skin breakdown• Infection control, wound care

SSS treatment and complications

• Start empiric IV: PCNase resistant PCN, 1st or 2nd gen cephalosporin, and/or clindamycin

• Further therapy based on culture and sensitivities

• Clarithromycin and cefuroxime with PCN allergy

• Not improving/critically ill, consider Vancomycin

• Uncommon complications: sepsis, pneumonia, cellulitis, dehydration, hypothermia, electrolyte imbalance

SSSS: updates to current practice

• Clindamycin initiation not associated with decreased LOS or improved outcomes#

• Clindamycin monotherapy is not recommended due to increasing resistance patterns (*up to 52% of SSSS patients)

• Spectrum of presentations^

*Braunstein et al. Pediatr Dermatol. 2014^Mazzori et al. CED. 2019

#Wang et al. Pwdiatr Dermatol 2020

Streptococcal skin infections (with AD)• Bacterial colonization/infection is higher in AD flares• Correlates with severity of skin lesions• Strep as a pathogen in poorly controlled AD*• Thick pustules and crusts with GAS, pain^• Facial and periorbital >>>> GAS than S. aureus (3.4X likely febrile)^• Higher rate of hospitalization (3X more than with SA)^• GAS+ were 3.7X more likely to have invasive infections• Mixed infections with S. aureus are common

*Arkwright PD et al. Arch Dermatol 2002*Adachi J et al. J Dermatol Sci 1998

*Hayakawa K et al. Clin Exp Dermatol 2009^Sugarman JL et al. Pediatr Dermatol 2011

GAS infections (with AD), take homes

• “Emerged” pathogen in skin and soft tissue infections, and AD• More likely to be sicker kids in the hospital with fever• Often co-cultured with staph aureus • Importance of culture and sensitivities • Prior to initiation of therapy• Consider when choosing empiric therapy

• Be on alert for more invasive infections with streptococcus• Consider in acutely worsening AD patients

“Eczema Coxsackium (EC)” and other atypical findings of hand, foot and mouth disease• Caused by cocksackie virus A6• High fever and often severe cutaneous lesions common• Accentuated in eczematous areas (eczema coxsackium)• Vesiculobullous and erosive eruption• Perioral, extremity and truncal involvement in addition to classical

HFMD areas (palms/soles/buttocks)• Accentuation in areas of previous skin injury (diaper rash, sunburn)

Mathes E. et al. Pediatrics 2013

Forms of HFMD

• Diffuse form (lesions extending to trunk) (all ages)• Classic acral form (infants, <2 years)• Eczema cocksackium-on preexisting eczema areas (2 years and older)• Other morphologies:• Petechial/purpuric form• Blistering form• Gianotti-crosti-like

• Sequelae: acral peeling and nail changes

Mathes E. et al. Pediatrics 2013

These atypical eruptions could be confused with other dermatoses:• Bullous impetigo• Eczema herpeticum• Vasculitis• Auto-immune bullous disease

Diagnosis and treatment

• High suspicion with symptoms of HFMD and cutaneous findings• Genotyping of coxsackie virus• PCR on swabs of skin vesicles, oropharynx, perirectal skin, stool or blood

• Respiratory PCR for enterovirus can help support• Rule out HSV when indicated, bacterial cultures• Supportive care, minimal need for hospitalization• Self-limited

Mathes E. et al. Pediatrics 2013

COVID-19 and the science of a pandemic • 93, 831 articles indexed in pubmed as of 1/31/21• 340 under search term “cutaneous” in “LitCOVID”

• 16 if add “pediatric” to search terms

https://www.ncbi.nlm.nih.gov/research/coronavirus/

Cutaneous manifestations associated with COVID-19 pandemic: review from literature (9/2020)

• Erythematous rash (morbilliform)—most commonly described

• Urticaria, urticaria-like rash• Trunk, often before onset of fever or respiratory symptoms

• Varicella-like papulovesicular exanthem

• Acral ischemic lesions, perniosis-like

• Others: livedo reticularis, petechial rash

• Kawasaki-like disease

Galli et al. Pediatr Allergy Immunol. 2020

Limitations:--May have other causes, co-infection--Descriptive--Also on medications--Lack of derm input, limited exam

Cutaneous features seen in children withCOVID-19: a review• Prevalence estimated between 0.025% and 3% in children/adolescents

• Most patients age 11-17 years, < male gender

• Most asymptomatic or few general symptoms

• Latency time from rash to symptoms: 1 day to weeks

• Lesions faded without sequelae

Khalili et al. Dermatol Ther. 2020

Types of skin lesions described in children (as of 9-2020)• Chillblain-like, acral erythema, acro-ischemia (1)• Erythema-multiforme-like• Dactylitis• Acute urticaria• Livedo reticularis, mottling (1)• Generalized maculopapular rash• Eyelid dermatitis (2)• Miliaria-like (1)• Varicelliform lesions (1)• Petechia and/or purpura

Khalili et al. Dermatol Ther. 2020

Pediatric patients with “COVID toes”

• Warm and cooler weather

• Explosion of cases with pandemic

• Positive contacts or asymptomatic, many tested negative• Low viral load, post-clearance of viremia or rapid clearance of virus

• Resolved without treatment after 7-10 days, no sequelae

• Differential diagnosis: lupus chilblain, perniosis, blue toes secondary to medications