What is causing this edematous facial deformity?

Facial Erysipelas—Double Dermatologic Danger

A 63-year-old physician (the author) noted 3 days of dark nasal discharge and obstructive crusting, followed by an abrupt illness with fever of 101ºF, chills, malaise, and asthenia. Within 3 hours, he could barely walk and collapsed in bed with severe, crippling myalgias. Six hours later, pink-red erythema erupted in the cheeks (Figure 1) and spread rapidly to the nose, upper lip, forehead, and eyelids, with fiery red coloration and disfiguring induration (Figure 2). Tender elevated plaques resembling leather saucers covered bilateral malar regions and were accompanied by heat, edema, vesicles, pustules, and shiny peau de orange appearance (Figure 3). Advancing erythema demonstrated sharply demarcated borders (Figure 4).

The patient became irrational and combative with family members. He was admitted to an academic medical center. Long-term faculty members did not recognize their colleague of 20 years due to edematous facial deformity. In addition to the facial findings described, the remainder of the physical examination was normal. On the evening of admission, fever peaked at 105ºF as malaise and weakness worsened. White blood cell count was 19,600 per mm³ with left shift. C-reactive protein (CRP) was 16.7 mg/L (normal: <0.5). Severe facial erysipelas with probable toxin production from Streptococcus pyogenes was diagnosed. Ceftriaxone was initiated empirically to cover primary streptococcal rhinitis, secondary extension to facial tissues, and toxin production by invasive S pyogenes infection. Concern remained for development of cavernous sinus thrombosis or other complication. 

Figure 1. Early hours of erythema of nose, cheeks, lip, and forehead.

Figure 2. After 6 hours, intense fiery erythema and induration involving entire face.

Within 24 hours of treatment with ceftriaxone 1 gmIV, fever nearly resolved, myalgia and misery receded, and vigor gradually returned. Facial erythema and edema, however, did not recede, but rather intensified centrally despite remaining within original borders ink marked at admission. Oral prednisone, 30 mg, was administered for anti-inflammatory effect.

Combination antibiotic and steroid therapy was accompanied by steady clinical improvement. By discharge on day 3, all systemic symptoms faded markedly, and extensive desquamation followed (Figure 5). Oral amoxicillin, 500 mg, 3 times daily, and prednisone 30 mg daily, were continued for an additional week. Within 10 days, return of healthy facial features was noted (Figure 6). No sequelae were observed. Three blood cultures yielded no growth.

Clinical manifestation. Erysipelas (erys, red; pelas, skin) is an abrupt-onset febrile condition affecting primarily the epidermis and superficial lymphatics of the face or extremities. Historically referred to as “St. Anthony’s fire,”¹ this illness is named after the medieval monk renowned for his healing powers over dread skin diseases. In modern times, erysipelas of the face is regarded as a rare, but serious infectious syndrome related to Group A beta-hemolytic streptococci, particularly S pyogenes, aggressively dispersing within superficial layers of facial skin, but occasionally threatening invasion of the CNS.^2,3 Unrestrained dermal and lymphatic proliferation of S pyogenes organisms gives rise to doubly dangerous pathogenesis: rapidly expanding invasive bacterial infection and streptococcal exotoxin production.⁴ Timely clinical intervention necessarily addresses both of these disease mechanisms in the management of this often explosive illness.

Facial erysipelas is an alarming infectious process, as depicted in this case. Interwoven and simultaneous infectious conditions involve invasive pathogens, toxin production, and potential for contiguous spread to vital intracranial structures within the central nervous system.^4,5 Group A beta-hemolytic S pyogenes is documented in most cases. Other streptococcal species from Groups B, C, F, and G have been infrequently implicated.⁶ For example, among a series of 229 hospitalized patients with erysipelas in Sweden, 78 cases (34%) were attributed to beta-hemolytic streptococci, mainly Group A strains.⁷  All 3 patients with facial erysipelas in this cohort were found to have nasal or throat colonization with Group A streptococcus. Furthermore, in a study of 27 patients with classic erysipelas, 26 had evidence of streptococcal infection, predominantly Group A, which was detected in 13 of 19 cases tested.⁸ 

Figure 3. Malar plaques, vesicles, pustules, and peau de orange edema of cheeks and nose.

Figure 4. Sharp demarcation.

Histologically, erysipelas is characterized by marked subepidermal edema, vascular dilation, dense infiltrates of polymorphonuclear neutrophils and lymphocytes, and streptococcal invasion of superficial lymphatics and connective tissues.4 Vesicles and pustules are toxin-mediated indicators of greater disease severity and are sterile on culture.

Explosive subcutaneous infection of the face has been attributed to streptococcal nasal colonization and deeper invasion from antecedent rhinosinusitis within the nasopharynx. In clinical practice, facial erysipelas has become relatively rare, with only 5% to 20% of contemporary cases arising on the face. Focal involvement of lower extremities is more frequent, perhaps due to rising geriatric trends in venous stasis, dermatitis, lymphedema, arterial disease, diabetic ulcers, or other lower leg conditions.⁷ Furthermore, a retrospective chart review of 529 patients with erysipelas hospitalized in France documented a 12.5% incidence of facial infection.⁸

Pyogenic exotoxin produced by most strains of Group A streptococci is responsible for many of the expansive systemic features of erysipelas. Parallels have been described between toxin-mediated symptoms and signs in erysipelas and similar manifestations seen in other febrile rash syndromes such as scarlet fever and streptococcal toxic-shock syndrome. Toxic mediators implicated in systemic symptoms observed in erysipelas include cytokines such as tumor necrosis factor (TNF)-alpha and TNF-beta, interleukin (IL)-1 beta, IL-2, IL-6, and interferon gamma.^8,9

Differential diagnosis. The fiery erythema, well-demarcated border, and raised indurated plaques seen in erysipelas may generate diagnostic confusion with another infectious dermatologic condition—cellulitis.¹⁰ See Table for comparison. Major differences favoring cellulitis include isolation of staphylococcal organisms (not streptococci) in cellulitis, dull crimson erythema (instead of fiery redness), vague borders (poorly demarcated), absence of edema and lymphatic involvement (instead of indurated, raised plaques), and tendency to arise on trunk or extremities (not the face). In addition, cellulitis, unlike erysipelas, involves deeper subcutaneous tissues and may even generate frank purulence or abscess formation. While the onset of erysipelas is typically sudden, with fever, chills, fatigue, myalgia, and malaise, cellulitis tends to be more indolent and often is a complication of existing epidermal injury or chronic limb edema.

Figure 5. Desquamation during convalescence.

Figure 6. Return of normal facial features in 10 days.

Apart from cellulitis, facial erysipelas shares clinical features with a number of other dermatologic disorders.¹⁰ Diagnostic evaluation must consider contact dermatitis, rosacea, herpes zoster, erythema migrans, systemic lupus erythematosus, angioedema, metastatic inflammatory breast cancer (carcinoma erysipelatoides), and necrotizing fasciitis. Nonetheless, the constellation of indurated facial plaques, lymphatic edema, demarcated “butterfly” distribution of facial erythema, and sudden systemic symptoms is strongly suggestive of erysipelas.

Treatment. Prompt infusion of parenteral antibiotics effective against Group A beta-hemolytic streptococcal infection is essential. Penicillin G is the historic drug of choice for S pyogenes.¹¹ Administered as 2,000,000 units IV every 6 hours, penicillin G requires dosing at least 4 times per 24 hours. Ceftriaxone, in contrast, was chosen in this case since it is effective against most streptococci and necessitates infusion only once or twice daily due to its extended half-life. Other parenteral options include erythromycin, clindamycin, cefazolin, and vancomycin. Roxithromycin, a macrolide, and pristinamycin, a streptogramin, are oral alternatives utilized in Europe and effective against streptococci.^12,13 Duration of antibiotic therapy is 5 to 10 days depending on therapeutic response and may be switched from parenteral to oral as illness recedes.

Dramatic resolution of most systemic symptoms may be observed within 24 to 36 hours, as was noted in this patient. Paradoxic worsening of facial erythema and edema, as is also described in this case, is attributed to slow eradication of dermal pathogens and delayed termination of exotoxin production. 

Anti-inflammatory agents in conjunction with penicillin have been evaluated in moderate-to-severe erysipelas. Significant benefits have been demonstrated in elimination of toxin production, reduction in recovery time, decreased antibiotic requirements, and shortening of hospitalization. Two regimens with statistically significant benefit in published clinical trials include prednisolone 30 mg orally in tapered dose for 8 days, and ibuprofen 400 mg orally every 6 hours for 5 days.^14,15 The 2014 guidelines from the Infectious Disease Society of America recommend parenteral penicillin for moderate-to-severe erysipelas and indicate that corticosteroids (prednisone 40 mg daily for 7 days) “could be considered in nondiabetic adult patients” as adjunctive therapy.¹¹

Complications. Delayed or mistaken diagnosis of facial erysipelas may result in unfavorable outcomes for a syndrome, which typically responds rapidly and completely to timely therapy. Reported complications include cavernous sinus thrombosis (CST), sepsis, meningitis, necrotizing fasciitis, post-streptococcal glomerulonephritis, and death during pregnancy.¹⁶

CST is a particularly worrisome sequelae of central facial infections involving the “danger triangle of the face” inscribed by a 3-sided anatomic zone from the corners of the mouth to the bridge of the nose.¹⁷ Normal facial veins drain caudally through this triangle into dural sinuses which straddle the sella turcica and empty into the internal jugular veins. Compact juxtaposition of cavernous sinus veins, internal carotid arteries, third, fourth, fifth, and sixth cranial nerves, and webs of paranasal sinuses provides an anatomic setup for infection and clot formation at the base of the brain. Close proximity of these CNS structures to aggressive, spreading, thrombogenic, midface infection predisposes to CST. Manifestations of central venous obstruction suggestive of CST include headache, fever, exophthalmos, periorbital edema, and extraocular palsies, particularly lateral gaze palsy. Physical examination may reveal the presence of a nasal furuncle, sphenoid or ethmoid sinusitis, or dental infection, any of which could serve as a suitable streptococcal portal of entry. In fact, the crusted rhinitis noted at the outset of this case, in retrospect, was likely of streptococcal origin. The fulminant nature of CST carries high morbidity and mortality depending on severity at time of detection and promptness of administration of parenteral antibiotics. Systemic anticoagulation, thrombolytic therapy, and adjunctive corticosteroids are controversial additions to anti-infective agents in the management of CST.¹⁸

Table. Erysipelas vs Cellulitis

Conclusion. Invasive streptococcal infection of the facial soft tissues creates dramatic and explosive double danger for physician and patient, specifically: infectious manifestations of S pyogenes and toxic activation of cytokines, as demonstrated in the case presentation. 

The marked elevations of the white blood cell count and CRP were indicative of the serious infectious and inflammatory acuity portrayed in the case described and required prompt, aggressive management. Penicillin and ceftriaxone remain dependable modern antibiotic weapons against most beta-hemolytic streptococci, while corticosteroids blunt or eliminate systemic symptoms of toxicity. A parenteral third-generation cephalosporin and oral steroids provided impressive relief for this patient, without setback.

Retrograde extension of central facial infection into contiguous CNS structures may lead to CST with its high morbidity and mortality.¹⁷ Clinical familiarity with the dynamic nature of facial erysipelas, as portrayed in the case presentation, allows prompt recognition, accurate diagnosis, precise therapy, reduction in risk of complications, and rewarding response to emergent management of this dangerous dual dermatologic disorder.¹⁹

Acknowledgment

The author is grateful to Bruce M. LeClair, M.D., and John F. Fisher, M.D., for helpful manuscript insights.

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