1000-2000 5 ьшò

involvement)

Lupus (of the face; less fever, positive antinuclear antibodies)

Polychondritis (common site is the ear) Other bacterial infections to consider:

–Meat, shellfish, fish, and poultry workers: Erysipelothrix rhusiopathiae (known as erysipeloid)

–Human bite: Eikenella corrodens

–Cat/dog bite: Pasteurella multocida/Capnocytophaga canimorsus

–Salt water exposure: Vibrio vulnificus

–Fresh/brackish water exposure: Aeromonas hydrophila

DIAGNOSTIC TESTS & INTERPRETATION

Reserve diagnostic tests for severely ill, toxic patients, or those who are immunosuppressed.

Initial Tests (lab, imaging)

Leukocytosis

Blood culture (<5% positive)

Elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)

Streptococci may be cultured from exudate/noninvolved sites.

Test Interpretation

Biopsy is not needed; however, skin findings would show

Dermal and epidermal edema, extending into the SC tissues

Peau d’orange appearance caused by edema in the superficial tissue surrounding the hair follicles

Vasodilation and enlarged lymphatics

Mixed interstitial infiltrate mainly consisting of neutrophils and mononuclear cells

Endothelial cell swelling

Gram-positive cocci in lymphatics and tissue with rare invasion of local blood vessels

Fibrotic thickening of lymphatic vessel walls with possible luminal occlusion may be seen in recurrent erysipelas.

TREATMENT

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GENERALMEASURES

Symptomatic treatment of myalgias and fever

Adequate fluid intake

Local treatment with cold compresses

Elevation of affected extremity

Appropriate therapy for any underlying predisposing condition

MEDICATION

Antibiotics cure 50–100% of infections, but which regimen is most successful is unclear.

Antibiotics may be as effective when given orally versus intravenously.

A5-day course of antibiotics may be as effective as a 10-day course at curing (4)[A].

First Line

Adults

–Extremities, nondiabetic Primary

■Penicillin G: 1 to 2 million U IV q6h or cefazolin 1 g IV q8h

Alternative (if penicillin-allergic)

■Vancomycin 15 mg/kg IV q12h

■When afebrile Pen VK 500 mg PO QID AC and HS

–Total 10 days, diabetics Early-mild:

■Trimethoprim-sulfamethoxazole (TMP-SMX)-DS: 1 to 2 tabs PO BID and penicillin VK 500 mg PO QID or cephalexin 500 mg PO QID

–Severe disease

IMPor MER or ERTAIV and linezolid 600 mg IV/PO BID or vancomycin IV or daptomycin 4 mg/kg IV q24h

–Facial

Primary

■Vancomycin: 15 mg/kg (actual weight) IV q8–12h with target trough

15 to 20 Alternative

■ Daptomycin 4 mg/kg IV q24h or linezolid 600 mg IV q12h Children

–Penicillin G

0 to 7 days, <2,000 g = 50,000 U/kg q12h

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8 to 28 days, <2,000 g = 75,000 U/kg q8h

0 to 7 days, >2,000 g = 50,000 U/kg q8h

8 to 28 days, >2,000 g = 50,000 U/kg q6h >28 days = 50,000 U/kg/day

–Cefazolin

0 to 7 days, <2,000 g = 25 mg/kg q12h

8 to 28 days, <2,000 g = 25 mg/kg q12h

0 to 7 days, >2,000 g = 25 mg/kg q12h

8 to 28 days, >2,000 g = 25 mg/kg q8h

>28 days = 25 mg/kg q8h

No reported group Astreptococci resistance to β-lactam antibiotics

In chronic recurrent infections, prophylactic treatment after the acute infection resolves:

–Penicillin G benzathine: 1.2 million U IM q4wk or penicillin VK 500 mg PO BID or azithromycin 250 mg PO QD

If staphylococcal infection is suspected or if patient is acutely ill, consider a β–lactamase-stable antibiotic.

Consider community-acquired MRSA, and depending on regional sensitivity, may treat MRSAwith TMP-SMX DS 1 tab PO BID or vancomycin 1 g IV q12h or doxycycline 100 mg PO BID.

ISSUES FOR REFERRAL

Recurrent infection, treatment failure

ADDITIONALTHERAPIES

Some patients may notice a deepening of erythema after initiating antimicrobial therapy. This may be due to the destruction of pathogens that release enzymes, increasing local inflammation. In this case, treatment with corticosteroids, in addition to antimicrobials, can mildly reduce healing time and antibiotic duration in patients with erysipelas. Consider prednisolone 30 mg/day with taper over 8 days.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

Admission criteria/initial stabilization

–Patient with systemic toxicity

–Patient with high-risk factors (e.g., elderly, lymphedema, postsplenectomy, diabetes)

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– Failed outpatient care

IV therapy if systemic toxicity/unable to tolerate PO

Discharge criteria: no evidence of systemic toxicity with resolution of erythema and swelling

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Bed rest with elevation of extremity during acute infection, then activity as tolerated

Patient Monitoring

Patients should be treated until all symptoms and skin manifestations have resolved.

PATIENT EDUCATION

Stress importance of completing prescribed medication regimen.

PROGNOSIS

Patients should recover fully if adequately treated.

May experience deepening of erythema after initiation of antibiotics

Most respond to therapy after 24 to 48 hours.

Mortality is <1% in patients receiving appropriate treatment.

Bullae formation suggests longer disease course and often indicates a concomitant S. aureus infection that may require antibiotic coverage for MRSA.

Chronic edema/scarring may result from chronic recurrent cases.

Rarely, obstructive lymphadenitis may result from chronic recurrent cases.

COMPLICATIONS

Recurrent infection

Abscess (suggests staphylococcal infection)

Necrotizing fasciitis

Lymphedema (most prominent risk factor for recurrence) (5)

Bacteremia, which may lead to sepsis

Pneumonia (due to sepsis/toxin-producing organism) Meningitis (due to sepsis/toxin-producing organism)

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Embolism

Gangrene

Bursitis, septic arthritis, tendinitis, or osteitis

REFERENCES

1.Gabillot-Carré M, Roujeau JC. Acute bacterial skin infections and cellulitis. Curr Opin Infect Dis. 2007;20(2):118–123.

2.Celestin R, Brown J, Kihiczak G, et al. Erysipelas: a common potentially dangerous infection. Acta Dermatovenerol Alp Pannonica Adriat. 2007;16(3):123–127.

3.Breen JO. Skin and soft tissue infections in immunocompetent patients. Am Fam Physician. 2010;81(7):893–899.

4.Morris AD. Cellulitis and erysipelas. BMJ Clin Evid. 2008;2008:1708.

5.Inghammar M, Rasmussen M, Linder A. Recurrent erysipelas—risk factors and clinical presentation. BMC Infect Dis. 2014;14:270.

ADDITIONALREADING

Gilbert D, Chambers HF, Eliopoulos GM, et al, eds. The Sanford Guide to Antimicrobial Therapy. 44th ed. Sperryville, VA: Antimicrobial Therapy; 2014.

CODES

ICD10

A46 Erysipelas

CLINICALPEARLS

Athlete’s foot is the most common portal of entry.

Erysipelas is distinguished from cellulitis by its sharp, shiny, fiery-red, raised border.

In recurrent cases, search for other possible source of streptococcal infection (e.g., tonsils, sinuses, intertrigo).

Most erysipelas infections now occur on the legs, rather than the face.

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ERYTHEMAMULTIFORME

Losika Sivaganeshan, MD, MPH Pradeepa P.

Vimalachandran, MD, MPH

BASICS

Erythema multiforme (EM) is relatively common, acute, recurrent, selflimiting inflammatory disease.

–Mostly (~90% of cases) triggered by infectious agents (up to 50% by herpes simplex virus [HSV]-1 or -2), or less commonly, by drugs and vaccinations (1,2)

–Skin lesions include acrally distributed, distinct targetoid lesions with concentric color variation, sometimes accompanied by oral, genital, or ocular mucosal lesions (1,3).

–Flat, atypical lesions and macules with or without blisters are more suggestive of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (4,5).

There are no universal diagnostic criteria, but clinical history, clinical examination, skin biopsy, laboratory studies, and special consideration of persistent EM are all included in making a diagnosis.

DESCRIPTION

Two subtypes, erythema multiforme minor (EMm) and erythema multiforme major (EMM), with the former involving none or one mucous membrane, and the latter involving at least two mucous membrane sites. EMM is now separate from SJS and TEN.

Recurrent EM is defined as >3 attacks but has a mean number of 6 attacks (range 2 to 24) per year and a mean duration of 6 to 9.5 years (range 2 to 36) (1).

EPIDEMIOLOGY

Incidence

Annual U.S. incidence is estimated at <1% (1).

Prevalence

Peak incidence in 20s and 40s; rare <3 years and >50 years of age

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Slight male predominance is observed.

ETIOLOGYAND PATHOPHYSIOLOGY

The exact pathophysiology of EM is incompletely understood but appears to be the result of a TH1-mediated immune response to an inciting event such as infection or drug exposure.

Genetic susceptibility can be a predisposing factor in some patients with EM. Different HLAalleles have been found to be consistent in patients with EM.

HSV containing a certain HSV pol, a polymerase associated with the HSVtriggered EM seems to involve autoimmune activation (1).

With electron microscopy, there is evidence of lichenoid inflammatory infiltrate and epidermal necrosis including circulating immune complexes, deposition of C3, IgM, and fibrin around the upper dermal blood vessels.

SJS and TEN have an increased granulysin and perforin expression within T cells than in EM (4,5).

Previous viral infections, particularly; also Epstein-Barr, coxsackie, echovirus, varicella, mumps, poliovirus, hepatitis C, cytomegalovirus, HIV, molluscum contagiosum virus (1)

Bacterial infections, particularly Mycoplasma pneumoniae; other reported bacterial infections include Treponema pallidum, Mycobacterium tuberculosis and Gardnerella vaginalis (1).

Medications, including NSAIDs, antibiotics, penicillin, sulfonamides, and antiepileptics (1,3)

Vaccines: stronger association with HPV, MMR, and small pox vaccines, but also associated with hepatitis B, meningococcal, pneumococcal, varicella, influenza, diphtheria-pertussis-tetanus, and H. influenzae (2)

Occupational exposures: herbicides (alachlor and butachlor), iodoacetonitrile

Radiation therapy

Premenstrual hormone changes (3)

Malignancy (3)

Genetics

Strong association with HLA-DQB10301, particularly in herpes-related cases (1); possible association in recurrent cases with HLA-B35, -B62, -DR53

RISK FACTORS

Previous history of EM

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GENERALPREVENTION

Known or suspected etiologic agents should be avoided.

Acyclovir or valacyclovir may help prevent herpes-related recurrent EM.

COMMONLYASSOCIATED CONDITIONS

See “Etiology and Pathophysiology” earlier.

DIAGNOSIS

Clinical

HISTORY

Absent or mild prodromal symptoms

Acute, self-limiting, episodic course

History of new medication

Preceding HSV infection 10 to 15 days before the skin eruptions

Rash involving the skin and sometimes the mucous membrane, most commonly the mouth.

Symptoms of any of the infections associated with EM, most commonly HSV and M. pneumoniae

PHYSICALEXAM

Acral extremities

Symmetric cutaneous eruptions composed of targetoid lesions with concentric color variation

Mucosal involvement

–Oral involvement manifests as erythema, erosions, bullae, and ulcerations on both nonkeratinized and keratinized mucosal surfaces and on the vermilion of the lips; minimal involvement in EMm, if present, most commonly involves the mouth

–Can include any mucosal tissue including genital, ocular, oral, and so forth

–At least two mucosal sites involved in EMM, including eyes (conjunctivitis, keratitis); mouth (stomatitis, cheilitis, characteristic blood-stained crusted erosions on lips); and probable trachea, bronchi, GI tract, or genital tract (balanitis and vulvitis) (5)

DIFFERENTIALDIAGNOSIS

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SJS

–Generalized distribution of lesions; concentrated on the trunk

–Macular atypical targetoid lesions

–Flat target lesions or macules with coalescence of lesions

–Blisters and skin detachment <10% of the total body surface area (5)

–1–5% mortality

–Presence of constitutional symptoms with presence of high fever (>38.5°C) more likely with SJS than EM

–More likely to have mucosal involvement at ≥2 sites, lymphadenopathy, high C-reactive protein levels (>10 mg/dL), and hepatic dysfunction, and

>90% have severe mucosal involvement at least at one site (1) TEN

–Similar to SJS but has full-thickness skin necrosis and skin detachment >30% of the total body surface area (5,6)

–34–40% mortality rate

Urticaria

Fixed drug eruption

Bullous pemphigoid

Paraneoplastic pemphigoid

Sweet syndrome

Rowell syndrome

Polymorphous light eruption

Cutaneous small-vessel vasculitis

Mucocutaneous lymph node syndrome

Erythema annulare centrifugum

Acute hemorrhagic edema of infancy

Subacute cutaneous lupus erythematosus

Contact dermatitis

Pityriasis rosea

HSV

Secondary syphilis

Tinea corporis

Dermatitis herpetiformis

Herpes gestationis

Septicemia

Serum sickness

Viral exanthem

Rocky Mountain spotted fever

Meningococcemia

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Lichen planus

Behçet syndrome

Recurrent aphthous ulcers

Herpetic gingivostomatitis

Granuloma annulare

DIAGNOSTIC TESTS & INTERPRETATION

No lab test is indicated to make the diagnosis of EM (1).

Skin biopsy of lesional and perilesional tissue in equivocal conditions

Direct and indirect immunofluorescence (DIF and IIF) to differentiate EM from other vesiculobullous diseases. DIF is detected on a biopsy of perilesional skin, and IIF is detected from a blood sample (1).

HSV tests in recurrent EM (serologic tests, swab culture, or tests using skin biopsy sample to check HSV antigens or DNAin keratinocytes by DIF or direct fluorescent antibody [DFA] or polymerase chain reaction [PCR])

Antibody staining to IFN-γ and TNF-α to differentiate HSV from drugassociated EM

As the second most common cause of EM, M. pneumoniae should be worked up with CXR, swabs, and serologic test.

In persistent EM, check complement levels (1).

Initial Tests (lab, imaging)

No imaging studies are indicated in most cases unless there is suspicion for M. pneumoniae.

Follow-Up Tests & Special Considerations

Chest x-ray may be necessary if an underlying pulmonary infection (M. pneumoniae) is suspected.

Test Interpretation

Vacuolar interface dermatitis with CD4+ T lymphocytes and histiocytes in papillary dermis and the dermal–epidermal junction

Superficial perivascular lymphocytic inflammation

Satellite cell necrosis

Necrotic keratinocytes mainly in the basal layer Papillary dermal edema

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