Dermatologic Emergencies: Rapid Response by the Pharmacist

Pharmacy TimesMay 2012 Skin & Eye Health
Volume 78
Issue 5

With some skin conditions, a rapid response by the pharmacist could mean the difference between life and death.

With some skin conditions, a rapid response by the pharmacist could mean the difference between life and death.

Fortunately, it’s rare to encounter patients with extensive or unusually painful skin conditions. These afflictions represent some of the most misery-creating medical problems ever seen. Unlike garden-variety rashes, lifethreatening skin diseases may weep, crust, and rot—eventually turning an intact, protective dermis into a leaky covering that allows infection to cause systemic damage. Many of these diseases are iatrogenic, and often, it’s the patient’s most recent prescription that causes the crisis.

Emergency cases in dermatology require immediate hospitalization, possibly in the intensive care unit. Although rare, many of these cases are associated with high mortality, severe complications, and potential chronic disability.


Similar to but far more serious than hives, angioedema is a well-demarcated area of swelling subsequent to increased vascular permeability that can occur in the skin and the gastrointestinal and respiratory tracts. It can be acquired, but in rare cases it is autosomal-dominant heredity that causes C1INH deficiency and allows spontaneous activation of the complement system. As a dermatologic condition, it usually occurs in the face, extremities, or genitalia. It can progress to generalized anaphylactic reaction with upper airway compromise. Approximately half of cases are accompanied by itching, and almost all patients report burning.

Many cases are idiopathic; allergens like peanuts and medications cause this condition as well. Angiotensinconverting enzyme (ACE) inhibitor therapy has been associated with angioedema in 1 to 2 per 1000 new users, especially African Americans. Penicillins, nonsteroidal anti-inflammatory drugs (NSAIDs) (including aspirin), acetaminophen, and radiographic contrast media have also been implicated.1-4

Treatment begins with ensuring airway patency. Burning often decreases with cool, moist compresses and antihistamines. If the episode seems related to a specific allergen, referral to an allergy specialist is critical. Avoidance of known triggers, such as associated medications, is paramount. Patients who have hereditary angioedema must avoid ACE inhibitors. Patients may generate more active C1INH, thereby reducing occurrences, if they take an androgen (danazol and stanozolol).1,4

Necrotizing Fasciitis

Necrotizing fasciitis is an aggressive, gas-producing infection of the deep fascia— the fibrous connective tissue separating or binding muscles and organs— that causes subcutaneous tissue necrosis; it occurs in 2 distinct types.5,6 Since 2005, necrotizing fasciitis’s incidence has increased markedly. Specialists consider it an emergency because of its aggressive nature, the spectrum of pathogens involved, and the high likelihood of limb loss or death (~24%).

Type I’s hallmark is mixed pathogens— an average of 4 mixed anaerobes, Gram-negative aerobic bacilli, and enterococci. Type I typically begins in an existing but indolent site, usually a perirectal infection, colonic lesion, intravenous drug injection site, trauma, chronic diabetic ulceration, and/or other skin infection. Less frequently, a single, more virulent pathogen (usually group A streptococci) will produce exotoxins that cause rapidly progressive necrosis; this is Type II necrotizing fasciitis.7

In both types of necrotizing infections, patients will report pain that is far more serious than observation of the lesions would suggest probable.7 Most symptoms occur late, so clinicians need to maintain a high index of suspicion. Diffuse swelling is followed by development of bullae that become burgundy quickly. Other signs include crepitation (crackling at touch), muscle weakness, and foul-smelling exudates. Gangrene can develop, complicating the picture.

The presentation of this complicated skin and soft tissue infection may differ in patients who have a serious underlying disease, previous hospital admissions, animal contact and bite history, history of injectable drug use (especially methamphetamine, which is closely associated with methicillinresistant Staphylococcus aureus), or recent travel.6,8 Treatment includes immediate and appropriate antibiotic therapy and skilled surgical debridement with constant vigilance for shock and organ failure.5-8

Rocky Mountain Spotted Fever

Usually the result of a tick bite, Rocky Mountain Spotted Fever (RMSF) is an infection with the Rickettsia rickettsii parasite. Its name is a bit of a misnomer. It occurs in every US state except Hawaii (not just in the Rocky Mountains), but the rash is purpuric macules—in other words, it’s spotty.

Approximately 60% of patients present with fever, headache, and a classic rash on the wrists and ankles that rapidly spreads to the palms and soles and eventually to the trunk and face after a tick bite. This is called the RMSF “classic triad.” With immediate treatment, mortality is 3% to 7%. Without treatment or with inadequate treatment, mortality soars to 30% or higher. Complications include hepatic or renal failure, myocarditis and cardiogenic shock, altered mental status, seizures or coma, meningismus, and disseminated intravascular coagulation.9,10

At the first suspicion of RMSF, prescribers should start doxycycline. The drug should be continued until fever is gone for at least 3 days and the patient’s clinical condition is stable. Chloramphenicol is an alternative for pregnant women and doxyclineintolerant patients.9,10

Stevens-Johnson Syndrome

Stevens-Johnson Syndrome (SJS) is mucocutaneous reactions that cause the epidermis to separate from the dermis. SJS is a mild form of toxic epidermal necrolysis [TEN]; less than 10% of the epidermis sloughs off in SJS, whereas more than 30% will in TEN.) Most cases have no identified cause, but infections and medications including sulfonamides, anticonvulsants, allopurinol, and NSAIDs have been associated with SJS.11,13

Two factors seem to be at play: impaired ability to detoxify intermediate drug metabolites and genetic susceptibility. When drugs are at cause, patients generally started therapy 1 to 3 weeks before the rash appears.11 Mortality is estimated at 10% in SJS and 30% in TEN.13

SJS and TEN require expert management in an ICU. In addition to aggressive supportive care in a manner similar to that used with burn victims, prescribers should discontinue all possible offending medication. Patients will need temperature homeostasis and ophthalmologic assessment. Symptomatic treatment may include wound dressings, oral hygiene (ie, chlorhexidine rinses), antihistamine and topical corticosteroid therapy for itching, and antibiotics if superinfection occurs. Intravenous immunoglobulin has been used for TEN, but additional study is needed.11-13

Toxic Shock Syndrome

Originally identified in 1981 when a number of women developed a unique constellation of life-threatening symptoms that were eventually traced to high-absorbency tampon use, toxic shock syndrome (TSS; also called septic shock) is rapidly progressive.14 It’s generally caused by toxins produced by either staphylococci (usually S aureus) or streptococci (usually Staphylococcus pyogenes) that cause extensive cytokine release.14,15 Symptoms vary.

These serious symptoms often follow several days of malaise. Patients typically present with fever, chills, nausea, and abdominal pain. Death, however, can occur within hours. TSS rashes usually begin on the trunk and spread peripherally to the palms and soles. Cardiac arrhythmias, disseminated intravascular coagulation, and acute respiratory distress syndrome are possible.

Treatment must be aggressive and supportive. Fluid management is always needed and ventilation and organ support are often necessary. If the infection’s source is still present, it must be removed or drained. Antibiotic treatment with agents that cover S pyogenes and S aureus (cephalosporins, penicillins, or vancomycin) can be augmented with clindamycin or gentamicin to reduce mortality.17-19

Final Thought

Emergencies that manifest as serious skin diseases typically have high case fatality rates and serious consequences for patients. Pharmacists who see patients with rapidly progressive or extremely painful skin symptoms should refer them for emergency care immediately. Clinical decisions regarding therapy require skill and careful judgment—and the pharmacist must know how to respond to these serious cases.

SJS and TEN: A Quick Review

• Sometimes starts with fever, stinging eyes, and painful swallowing. Patients experience skin tenderness, erythema, epidermal necrosis, and desquamation.

• Dusky (blue to black) erythematous macules progress to flaccid blisters.

• Two or more mucous membranes are usually involved with buccal, genital, and ocular mucosa erythema and erosions.

• Massive fluid loss and electrolyte imbalance follows epidermal detachment. These conditions are potentially life-threatening because of their multisystem involvement and skin-barrier breakdown. Epithelial loss results in vulnerability to bacterial and fungal infections and predisposes patients to septicemia and severe fluid loss. Mortality ranges from 5% in SJS to 30% in TEN.

• Survivors may suffer from mucous membrane strictures.

• Severe ophthalmic involvement may lead to permanent scarring and blindness.

SJS = Stevens—Johnson Syndrome; TEN = toxic epidermal necrolysis. Adapted from references 11 and 12.

Symptoms of Toxic Shock Syndrome

• Temperature greater than 38.9oC (102oF)

• Systolic blood pressure less than 90 mm HG

• Generalized erythema or diffuse rash resembling sunburn with desquamation

• Organ system involvement (including mucous membrane hyperemia, renal failure, hepatic inflammation, thrombocytopenia, or central nervous system involvement

Adapted from reference 16.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.


1. Bowen T, Cicardi M, Farkas H, et al. Canadian 2003 international consensus algorithm for the diagnosis, therapy, and management of hereditary angioedema. J Allergy Clin Immunol. 2004;114:629-637.

2. Cugno M, Asero R, Tedeschi A, Lazzari R, Marzano AV. Inflammation and coagulation in urticaria and angioedema [published online ahead of print January 20, 2012]. Curr Vasc Pharmacol.

3. Mancia G, Schumacher H. Incidence of adverse events with telmisartan compared with ACE inhibitors: evidence from a pooled analysis of clinical trials. Patient Prefer Adherence. 2012;6:1-9.

4. Bernstein JA. Update on angioedema: evaluation, diagnosis, and treatment. Allergy Asthma Proc. 2011;32:408-412.

5. Elliott DC, Kufera JA, Myers RA. Necrotizing soft tissue infections: risk factors for mortality and strategies for management. Ann Surg. 1996;224:672-683.

6. Dryden MS. Complicated skin and soft tissue infection. J Antimicrob Chemother. 2010;65 (suppl 3):iii35-iii44.

7. Smeets L, Bous A, Heymans O. Necrotizing fasciitis: case report and review of literature. Acta Chir Belg. 2007;107:29-36.

8. Cohen AL, Shuler C, McAllister S, et al. Methamphetamine use and methicillin-resistant Staphylococcus aureus skin infections. Emerg Infect Dis. 2007;13:1707-1713.

9. Graham J, Stockley K, Goldman RD. Tick-borne illnesses: a CME update. Pediatr Emerg Care. 2011;27:141-147.

10. Minniear TD, Buckingham SC. Managing Rocky Mountain spotted fever. Expert Rev Anti Infect Ther. 2009;7:1131-1137.

11. Mockenhaupt M. The current understanding of Stevens-Johnson syndrome and toxic epidermal necrolysis. Expert Rev Clin Immunol. 2011;7:803-813.

12. Tremblay L, de Chambrun GP, De Vroey B, et al. Stevens-Johnson syndrome with sulfasalazine treatment: report of two cases. J Crohns Colitis. 2011;5:457-460.

13. Barvaliya M, Sanmukhani J, Patel T, Paliwal N, Shah H, Tripathi C. Drug-induced Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap: a multicentric retrospective study. J Postgrad Med. 2011;57:115-119.

14. Herzer CM. Toxic shock syndrome: broadening the differential diagnosis. J Am Board Fam Pract. 2001;14(2):131-136. PubMed PMID: 11314920.

15. Iwatsuki K, Yamasaki O, Morizane S, Oono T. Staphylococcal cutaneous infections: invasion, evasion and aggression. J Dermatol Sci. 2006;42:203-214.

16. Centers for Disease Prevention and Control. Case definitions for surveillance. Accessed January 27, 2012.

17. Zane S, Guarner J. Gynecologic clostridial toxic shock in women of reproductive age. Curr Infect Dis Rep. 2011;13:561-570.

18. Li J, Carr B, Goyal M, Gaieski DF. Sepsis: the inflammatory foundation of pathophysiology and therapy. Hosp Pract (Minneap). 2011;39:99-112.

19. Hanberger H, Giske CG, Giamarellou H. When and how to cover for resistant gram-negative bacilli in severe sepsis and septic shock. Curr Infect Dis Rep. 2011;13:416-425.

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