Rash (Vesiculobullous) & Fever
Approach to fever and rash
- Key elements of the history are: immune status, immunizations, exposures to ill person or animals or insects, travel history, sexual history, new meds, geography, season of year
- Focused physical on pattern of rash
- Pattern types include vesiculobullous, peripheral, central maculopapular, nodular, purpuric, urticarial, eschar, confluent desquamative etc
Immediately Life-Threatening Causes of Fever and Rash - "The Big Four"
Fever and rash carries a broad differential diagnosis, especially in immunocompromised patients (see below). Often times the etiology is not obvious and workup involves cultures, skin biopsy, serologies, etc. However, it is important to always consider these 4 syndromes below that can be rapidly fatal if not recognized and treated promptly, even if this is by no means an exhaustive list.
1. Meningococcemia with Purpura Fulminans – suspect in patients with signs of sepsis, meningitis and a petechiael or purpuric rash. The rash starts as skin pain, followed by erythema and petechiae, then ecchymoses that progress to painful, well demarcated and indurated purple patches. Eventually, this results in bullae and gangrenous necrosis. Treatment involves prompt recognition and antibiotics (and chemoprophylaxis for close contacts).
2. Toxic Shock Syndrome – most commonly due to Group A Strep and less often due to Staph aureus. Clinically, both present with acute onset of hypotension and multiorgan failure with a distributive shock physiology. Staph TSS more commonly has a diffuse erythematous rash that involves the palms and soles, and desquamates in 1-2 weeks if the patient survives; in Strep TSS, a diffuse scarlatina-like erythema is present in only ~10% of cases. In Strep TSS, bacteremia is much more common than in Staph TSS (~60% vs 5%), and prognosis is much much worse (>50% mortality vs ~5%). Treatment involves hemodynamic support, antibiotics (PCN and Clindamycin for Strep TSS), and surgical debridement for cases associated with necrotizing fasciitis. There is also limited data to support the use of IVIG.
3. Rocky Mountain Spotted Fever – infection with Rickettisa rickettsi, which is transmitted via ticks in the mid-Atlantic, New England, Midwest, southeast, Canada, Mexico, and parts of Central and South America, peaking in the spring and early summer. It presents with fever, headache, myagias/arthralgias, nausea/vomiting, and rash. The rash characteristically starts at the ankles and wrists, then spreads both to the palms and soles and centrally, starting as a maculopapular rash and turning petechial. Diagnosis can be made both clinically and by skin biopsy, as well as serologies; however, it is important to start treatment immediately with Doxycycline as this can be rapidly fatal.
4. Stevens Johnson Syndrome/Toxic Epidermal Necrolysis – presents with a prodrome of fever and influenza-like symptoms, then erythematous macules and plaques, that progresses to epiderma necrosis and sloughing, with mucous membrane involvement. SJS refers to when < 10% of the body surface area is affected; TEN refers to when > 30% BSA is affected (10-30% = SJS/TEN Overlap Syndrome). Far and away the most common cause is an idiosyncratic reaction to drugs, especially Allopurinol, Antibiotics (Sulfas and PCNs), Antipsychotics, Antiepileptics, and NSAIDs. Less commonly than drug reactions, in children it is sometimesassociated with infections such as Mycoplasma pneumonia and herpes viruses. Treatment is supportive (i.e. stop the offending drug, excellent wound care often in a burn unit, prevention of infections). Steroids and IVIG may be of slight benefit.
Of note, there exists controversy over whether or not Erythema Multiforme Major encompasses SJS; many now believe Erythema Multiforme to be of different pathogenesis, as it is mainly associated with infection with herpes viruses.
Differential for vesiculobullous rash and fever
A. Infectious vesicles:
- herpes- in single dermatome. pain precedes vesicles; lips, genitals, head and neck of wrestlers, digits of health care workers
- varicella- different stages of development
- variola- same stages of development
- rickettsialpox (transmitted by mite bites)- papule with central vesicle evolves into 1-2.5cm painless crusted black eschar with erythematous halo and proximal adenopathy. NE USA, AZ, OH, Utah
- pseudomonas aka hot tub folliculitus
- pseudomonas causing ecythma gangrenous in immunocompromised patients with disseminated bullae and sepsis
- coxsackie A16 vesicles on hands, feet and mouth of kids
- Orf - small pox related virus on fingers of ppl who tend goats and sheep
- molluscum contagious virus induces flaccid vesicles on skin of healthy and immunocompromised pts
Infectious bullae:
- SSSS in neonates d/t toxin
- nec fasc and gas gangrene
- scabies - bullous variant
- vibrio- exposure to gulf of mexico or atlantic seaboard or ingestion of raw seafood.
B. Autoimmune
- bullous pemphigoid (BP): blistering skin lesions due to auto ABs. typically flexural surfaces, groin and axillae. occurs in middle-aged to elderly. pruritis is common. can be bullae or urticarial plaques. IgG and C3 deposits in BM. Drug triggers penicillamine, captopril, furosemide
- pemphigus vulgaris (PV): starts in oral mucosa, spreads to face, axilla, groin. flaccid bullae. IgG deposits between epidermal cells
C. Drug reaction e.g TEN
D. Contact dermatitis
Biopsy will help distinguish between etiologies. Our patient underwent two biopsies, one near the edge of the lesion which is useful for direct immunofluoresence (DIF) and another within the lesion. The DIF permits visualization of immune complexes. PV will have a more diffuse staining within the epidermis while BP will have IgG to desmoplein at the dermal-epidermal junction.
Pearl: Patients with atopic dermatitis are at increased risk for staph infections.
Treatment of atopic dermatitis includes avoiding triggers, such as heat, perspiration, low humidity. In addition, skin infections should be treated and antihistamines used for sedation and control of itching. Treatment of stress and anxiety may also be necessary. Moisturize the skin with an emollient with a high oil content. Topical calcineurin inhibitors may be used if the patient has failed topical corticosteroids or in case of skin atrophy.
(Katharine Cheung MD, 4/10/11)
(Chanu Rhee MD, 6/3/11)