Patient with diffuse skin rash in the ICU

Synonyms

1. Description of the problem

What every clinician needs to know

Patients may present to the ICU with widespread skin lesions from multiple etiologies. Widespread eruptions or acute skin inflammation may be the primary problem leading to ICU admission or a cutaneous sign of a significant internal process, or may arise as a complication of management of a separate systemic disease. Patients in the ICU are at risk for developing numerous skin problems as a result of critical illness and the conditions required to care for acutely ill patients; these patients are at risk for developing line-related infections, allergic contact dermatitis to adhesives and leads, pressure necrosis and secondary herpetic infection from indwelling lines and endotracheal tubes, vasopressor-related vasculopathies, and more. Frequently patients in the ICU require substantial fluid resuscitation and may develop peripheral edema, complicated by malnutrition and secondary skin colonization and superinfection by commensal organisms and normal skin flora, such as candidal skin infections and dermatophytosis. A discussion of the multitude of cutaneous complications that may result in the critically ill patient is beyond the scope of this chapter.

This chapter will focus on a discussion of patients with a diffuse skin rash in the ICU, either as the cause of their admission or a complication of their ICU stay. Patients may have a widespread rash from multiple underlying etiologies. Assessment of the primary morphology is essential in narrowing the differential diagnosis and guiding the clinician towards making a specific diagnosis. As it may be challenging to elucidate the underlying etiology of a critically ill patient’s diffuse skin rash initially, upfront management will frequently require the clinician to treat multiple potential causes simultaneously.

Clinical features

Diffuse skin rash in the critically ill patient may manifest with multiple different morphologies and clinical presentations. This chapter will focus on the presentations most commonly seen in the ICU, with an emphasis on clues to recognizing different potential disease entities, early treatment and management, important diagnostic tests, and warning signs.

Morbilliform exanthems present with erythematous, blanchable macules and small papules, typically starting on the flanks, upper arms, and trunk. Lesions generally progress caudally, growing more confluent as they spread, often running together in broader erythematous patches. Lesions may show a predilection for sites of pressure, such as elastic waist bands, under leads, or under intermittent compression devices. Typically uncomplicated morbilliform rashes will not involve the mucosal surfaces, and in many cases the palms and soles will be spared. The differential diagnosis for triggers of a morbilliform rash is long, and it is frequently challenging to determine the precise underlying etiologic agent; the history is essential in making the correct diagnosis.

Cutaneous adverse drug reactions most often present with a typical morbilliform exanthem as described above. Morbilliform drug reactions typically occur 4-14 days after starting the offending agent. A personal or even family history of a reaction to a particular compound or class of agents may offer a clue, but prior reactivity is not necessary to attribute a morbilliform exanthem to a drug. While simple morbilliform drug reactions may be mild and limited to the skin, it is important to assess for systemic involvement. Acute interstitial nephritis may present with a variable rash that is most commonly described as morbilliform.

Drug reaction with eosinophilia and systemic symptoms (DRESS, formerly known as anticonvulsant hypersensitivity syndrome) may also present with a morbilliform rash initially. Patients with DRESS frequently have facial involvement, which is rare in uncomplicated morbilliform drug reactions. Additionally, patients with DRESS will often have lymphadenopathy and an abnormal CBC with either an elevated eosinophil count and/or atypical lymphocytes, and will frequently have elevated transaminases due to liver inflammation and hepatocellular damage. DRESS is notable as it may be a cause of ICU admission in and of itself, or it may complicate the course of a critically ill patient. Patients with DRESS may be severely ill, and there is a 10% mortality associated with this systemic adverse drug reaction. Patients may have myocarditis, acute renal failure, acute hepatic failure, and widespread multiorgan involvement.

A number of infections may present with a morbilliform rash. The list of viral infections that may present with a diffuse morbilliform skin rash is extensive and beyond the scope of this chapter. It is important to highlight certain infectious agents that may be associated with widespread morbilliform exanthems in the critically ill patient, however. Most notable among these is Rocky Mountain spotted fever (RMSF). RMSF is caused by Rickettsia rickettsii, transmitted by tick bites (typically Dermacentor variabilis, but Amblyomma americanum and Dermacentor andersoni may also act as vectors) in the US. Most frequently seen in spring and summer, and in the Eastern US, this disease typically presents one day to two weeks after a tick bite.

Patients often are significantly ill, with high fevers, chills, myalgias, and severe headaches. The cutaneous eruption typically starts a few days after the fever, with macules and small papules developing classically on the wrists and ankles, then progressing both centrifugally and centripetally to involve the palms, soles, and trunk and extremities. The face is generally spared. The lesions frequently develop a non-blanching, pinpoint, petechial component; some patients will develop frank purpura and gangrenous lesions as well, though this is rare. Typhoid fever, secondary syphilis, measles, viral hemorrhagic fevers, enteroviral infections, and dengue fever may all present with morbilliform exanthems; while there are subtle clues that may allow a skilled clinician to distinguish among them, it is important for the clinician to maintain a broad differential diagnosis when encountering a critically ill patient with a diffuse morbilliform rash of suspected infectious etiology.

Patients with acute graft-versus-host disease (AGVH) may also present with a morbilliform rash. The classic eruption of AGVH is one that begins on the face, particularly the forehead, cheeks, and ears, and often involves the neck, upper back, and chest. The blanchable red macules may develop preferentially around hair follicles, and close inspection is important to assess for perifollicular predominance. AGVH has a broad spectrum of disease, and may present with either limited skin involvement, mimicking a morbilliform drug reaction, or more widespread disease, such as in severe acute cutaneous graft versus host that can present with erythroderma (affecting more than 90% of the body) or even full-thickness epidermal necrosis from the most severe form of AGVH.

A history of organ transplant is essential in making the diagnosis; while GVH has been reported in patients who have received blood transfusions, autologous stem cell transplants, and solid organ transplants (particularly liver transplants, which contain many donor lymphocytes at the time of transplant), AGVH is typically seen in recipients of allogeneic hematopoietic stem cell transplants. The timing of transplant is important; AGVH can occur even well after transplantation, and post-transplant immunosuppressive regimens, tapering regimens, and any infections complications or disease flares may all trigger AGVH. Patients with AGVH may present with skin involvement alone, but it is important to assess all patients with suspected AGVH for liver and gastrointestinal involvement as well.

One final cause of widespread morbilliform rashes in the critically ill patient that should not be forgotten is miliaria, or heat rash. Patients with miliaria tend to develop erythematous macules, as well as papules, which may frequently appear excoriated; these lesions are typically concentrated on the back, in areas of heat, sweat, and occlusion. Generally miliaria is seen in febrile patients, but it may develop in any patients who are immobile for prolonged periods, as is common in the ICU. Clues are concentrations of lesions on the back, although miliaria may spread to the flanks and anterior abdomen, and intense pruritus; neither one of these is diagnostic. Miliaria tends to respond well to cooling the patient, encouraging frequent turnings, placing an absorbent pad or towel under the patient, and having the patient spend some time off of his or her back, ideally sitting upright, if possible.

The second key morphologic presentation of diffuse skin rash in the critically ill patient is erythroderma, or exfoliative dermatitis. Erythroderma manifests as widespread redness, usually blanchable, over 90% of the skin surface; this is often associated with a very fine, superficial scaling or desquamation of the topmost layer of the skin. Patients with erythroderma frequently have mild lymphadenopathy, are often uncomfortable and may have chills and rigors. Patients may develop significant fluid loss and electrolyte imbalances, require aggressive nutrition to maintain the rapid skin turnover, and are at risk for developing secondary skin infections and high-output cardiac failure and respiratory compromise. There are a number of conditions that may either present as, or progress to, erythroderma; while histopathologic evaluation of skin biopsies may be useful, once again a thorough history is critical in arriving at the correct diagnosis. Many cases are idiopathic, but more than half of cases of erythroderma are due to acute exacerbation of a preexisting condition.

Patients with atopic dermatitis may experience flares of their underlying disease that can present with widespread, even total-body inflammation, which may manifest as redness, erythema, and flaking. Patients with atopic dermatitis can develop fissures and cracking of the skin. Flares can result from noncompliance with medications, changes in skin care, or infection. Staphylococcal or streptococcal infection can trigger flares, or can complicate flares. Herpetic infection may be widespread in patients with abnormal skin barrier, and eczema herpeticum can present without the typical grouped vesicles of a standard HSV infection. Patients with eczema may develop widespread, subtle HSV, which can present as painful fissures, moist, purulent drainage from cracks and crevasses, or simply a painful, widespread flare of chronic eczema. Clues to a diagnosis of erythrodermic atopic dermatitis are primarily historical, although the presence of lichenification and dyspigmentation as a result of chronic scratching may suggest a history of longstanding underlying atopy.

Patients with psoriasis can develop erythroderma as well. Erythrodermic psoriasis may be indistringuishable from other forms of erythroderma, and eliciting a prior history of psoriasis is important. While stress, illness, and medications can contribute to psoriatic flares, every patient who presents with erythrodermic psoriasis should be evaluated for infection, as patients are frequently superinfected and may be bacteremic or septic. It may be difficult to distinguish patients with pustular psoriasis from those with erythrodermic psoriasis; presence of typical psoriatic lesions, a past history of psoriasis, nail pitting, or a diagnostic skin biopsy may be helpful in determining whether an erythrodermic patient has underlying psoriasis. Pityriasis rubra pilaris is an atypical psoriasiform disorder characterized by widespread, pink-orange erythema and fine scaling, often with distinctive “islands of sparing,” which typically involves the palms and soles with an orange-tinted keratoderma. Patients with severe seborrheic dermatitis may also appear erythrodermic; these patients frequently suffer from underlying immunocompromised states or neurologic disorders.

Certain infections can present with erythroderma. Staphylococcal scalded skin syndrome involves a primary infection by S. aureus capable of producing an exotoxin. Patients develop widespread skin erythema, which may be more pronounced in flexural areas; there are very superficial, flaccid bullae, which may resemble the type of desquamation seen after a severe sunburn. The areas of peeling are not full thickness, and while a Niklosky sign may be positive, there is usually intact epidermis even at sites of peeling. Mucosal surfaces are generally spared. Staphylococcal toxic shock syndrome rarely presents with erythroderma; this condition is characterized by fever, shock, and multiorgan failure. The skin manifestations are diffuse macular erythema, which may be more intense at the infected site; as patients improve, there is often desquamation of the palms and soles. Patients with streptococcal toxic shock usually have a skin infection (cellulitis, fasciitis, or traumatic wounds), and patients develop fever, shock, and multiorgan failure. The localized infected organ may be intensely painful, and a localized strep infection that develops violaceous discoloration with or without bullae, spreads rapidly, and is intensely painful is concerning for necrotizing fasciitis requiring immediate surgical evaluation.

Erythroderma due to cutaneous adverse drug eruptions is critical to recognize, as failure to withdraw the offending agent can contribute to ongoing inflammation and increased morbidity and mortality. The three main drug reactions for critical care physicians to consider in the case of a patient presenting with diffuse erythroderma in the ICU are Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). SJS/TEN will be discussed below, under widespread eruption with skin blisters. DRESS often presents with a widespread, sometimes confluent morbilliform exanthem that may favor the upper chest, back, and face, along with facial edema, lymphadenopathy, an abnormal CBC with atypical lymphocytes or eosinophils, and a transaminitis; patients may have fevers as high as 40C. This is usually a drug reaction that occurs weeks to months after starting a new medication; culprits include anticonvulsants, antibacterial sulfonamides, gold, minocycline, and others. Patients with DRESS can have systemic involvement beyond hepatocellular damage, and cases of myocarditis, pericarditis, and nephritis have been described. AGEP is characterized by widespread erythema and tiny, pin-sized pustules, which are often subtle and easily missed. Close skin inspection is essential. AGEP is usually attributable to a recent antibiotic, and often begins within 48 hours of medication initiation. Patients may be febrile and CBC may exhibit a peripheral neutrophilia. AGEP may be challenging to distinguish from widespread pustular psoriasis.

There are a number of less common entities that may present with diffuse erythroderma in the critical care setting. Patients may present with a diffuse erythroderma as a paraneoplastic syndrome, or as a manifestation of widespread cutaneous T-cell lymphoma. These patients may be acutely ill due to the underlying disease or a secondary infection. While autoimmune diseases such as lupus, dermatomyositis, and sarcoidosis have distinctive, classic cutaneous signs, an acute presentation may involve widespread erythroderma, and autoimmune diseases should remain on the differential diagnosis of patients presenting with a diffuse skin rash. Autoimmune blistering diseases, particularly pemphigus foliaceus and bullous pemphigoid, may rarely present with total-body erythroderma; clinicians may be aided in arriving at these diagnoses if there are areas with either adherent scale crusts at sites of ruptured, flaccid bullae in cases of PF, or urticarial plaques and intact tense bullae in the case of BP. Graft-versus-host disease generally presents in the skin with a morbilliform picture, often starting on the head, neck, upper back and chest, and displaying a preference for acral sites. Severe forms of acute GVH may present with erythroderma, and in patients with a history of transplantation, particularly if tapering immunosuppressive agents, infected, or suffering from hepatic or gastrointestinal symptoms, AGVH should be considered on the differential diagnosis of erythroderma.

It is important to remember that patients with crusted scabies, formerly known as Norwegian scabies, can present with widespread, near-total-body erythema and scaling. These patients are often incredibly pruritic, and frequently have areas of thick scaling, which in some cases may be concentrated on the palms and soles. Patients with crusted scabies are typically immunocompromised, and often have a history of exposure to the mite through living conditions, nursing home resident, or hospitalization.

The third morphologic lesion type that may be seen in a patient with a diffuse rash in the ICU is that of widespread skin failure or widespread skin blistering. The skin may blister at any level of the epidermis. Superficial blisters, below the stratum corneum or in the granular cell layer, may present with very flaccid, almost immediately rupturing blisters that look more like a superficial peeling eruption, or severe sunburn, rather than true blisters. Blisters deeper in the skin, either just above the basal layer or between the epidermis and dermis, may present with intact bullae or widespread sheets of epidermal sloughing, revealing beefy, moist dermis. Patients with widespread blistering eruptions or epidermal detachment are critically ill and require emergent, multidisciplinary care to diagnose and treat their cutaneous eruption. In severe cases, many of the causes of erythroderma may progress to frank blistering and epidermal detachment, and there is some overlap in the differential diagnosis.

While there are a number of rare subtypes, generally the autoimmune blistering diseases can be divided based on the antigen and antibody target, which determines the level of blister and the clinical manifestations. Patients with all of these disorders are managed with systemic immunomodulatory and immunosuppressive agents, and may present with infection due to iatrogenic immunocompromise or skin failure and secondary infection. Pemphigus foliaceus is due to antibodies against desmoglein 1, which causes cutaneous blisters and spares the mucosa. These patients may present with widespread skin lesions, which are often superficial, flaccid bullae that rupture and dry out, leading to a “cornflake”-like lesion adherent to the skin. Pemphigus vulgaris is due to antibodies against desmoglein 3 and/or 1, and often presents with mucosal erosions and deeper skin blisters, which may rupture and resemble widespread cutaneous erosions as well. Patients with bullous pemphigoid have deeper blisters, due to antibodies against the hemidesmosome, and often present with urticarial plaques and tense, intact bullae.

Blistering drug reactions are rare, but when these reactions develop patients are acutely ill and require ICU admission or transfer to either a critical care unit or burn center. Blistering drug reactions may be a cause for admission to the ICU, or complicate an ICU course. While almost any drug can cause a blistering eruption, antibacterial agents, antiepileptic drugs, NSAIDs, and allopurinol are frequently the culprits. SJS is defined as less than 10% body surface epidermal detachment, measured at the most extensive period of disease activity; TEN is defined as more than 30%, and when there is 10-30% detachment that represents an overlap between SJS and TEN. Patients with SJS/TEN often have two or more mucosal surfaces involved, are frequently systemically ill with fever, and are at risk for electrolyte imbalances, secondary infection and sepsis, and long-term sequelae from the loss of skin and mucosal barriers. It is essential to recognize these entities early, withdraw the offending agent, and initiate supportive care; therapy targeting the immune response is controversial and beyond the scope of this chapter.

Other notable causes of widespread rash with blistering include some entities previously described above, under the other morphologic types of widespread skin rash. Severe forms of AGVH may lead to blistering of the skin; these cases can mimic SJS/TEN and it is often challenging to distinguish between the two entities, particularly as patients with AGVH are often on multiple medications that may be associated with severe cutaneous adverse drug reactions. AGEP and generalized pustular psoriasis may appear to be blistering, as sometimes the small pustules will run together and appear as larger “lakes of pus,” mimicking widespread blistering. In these conditions, as in SSSS, the blisters are generally very superficial, leading to desquamation of the topmost layer of the epidermis, which when peeling reveals intact epidermis below. ICU staff should remember that allergic or irritant contact dermatitis can lead to blistering, in some cases including widespread blistering, and it is important to consider exposure history, as patients may react to various compounds, including surgical preps, skin-directed therapeutic agents, and adhesives.

The fourth morphologic subtype the may lead to diffuse skin rash in a patient in the ICU is palpable purpura, or a vasculitic lesion. These lesions clinically present with violaceous, deep red or purple papules that are non-blanching. Very active lesions may develop central necrosis or central bullae formation. This morphology tends to favor the extremities, and may run together to form confluent, non-blanching patches of violaceous discoloration. Patients may develop associated edema, and sometimes can have significant joint inflammation and swelling. Patients with widespread purpura may develop distal necrosis and gangrene as well, particularly of the digits, ears, and nose.

Patients with disseminated intravascular coagulation (DIC) due to underlying malignancy, clotting disorder, or infection can present with cutaneous lesions of petechiae, ecchymoses, purpura, or in some cases cutaneous necrosis, particularly involving the distal digits and extremities.

Meningococcemia is caused by Neisseria meningitidis. Patients usually present with signs of meningeal inflammation, fever, and, in severe forms, hypotension and shock. The skin lesions usually develop early on in the disease course, and are characterized by nonblanching pinpoint red petechieal macules and purpuric papules, which are generally small, irregularly shaped, angulated macules, which may develop raised areas of violaceous papules or hemorrhagic bullae. In widespread cases with disseminated purpura, DIC, and multiorgan failure, this may be called purpura fulminans. While other widespread severe infections may lead to diffuse purpura and cause purpura fulminans, meningococcemia is the classic example.

The differential diagnosis for widespread purpuric lesions in patients in the ICU also includes primary vasculitic disorders, including ANCA-positive vasculitis, widespread cutaneous small vessel vasculitis (which may occur as a primary process or as a secondary immunologic phenomenon due to infection or medication reactions), and vasoactive medication-related vascular changes.

Special note should be made of other conditions that may present with diffuse rash in the critically ill patient, including Kawasaki disease, gonococcemia, and necrotizing fasciitis; these entities should be considered in patients with an appropriate history and physical exam presenting to the ICU. Kawasaki disease occurs in children under 5; however, there are reports of cases in adults, particularly in patients with HIV. Kawasaki disease involves fever for 5 days, conjunctivitis, erythema of the tongue or oral mucosa, erythema and/or swelling of the hands or feet (which then desquamates), an erythematous rash, and cervical lymphadenopathy. Gonococcemia may present with joint pain and an associated hemorrhagic pustular rash, generally localized around the affected joint. Necrotizing fasciitis is discussed elsewhere at length; patients presenting with rapidly progressive, intensely painful skin erythema, fever, and septic physiology, particularly if there is overlying violaceous, dusky discoloration and/or blistering, should be evaluated for potential fascial infection.

Key management points

The essential management of patients in the ICU with a diffuse rash includes:

1. Supportive care and stabilization of the patient. Patients with widespread skin inflammation are at risk for high-output cardiac failure. Patients with skin failure often require aggressive IV fluid resuscitation, similar to burn victims. In states of rapid skin turnover and skin failure, electrolyte abnormalities are common and must be corrected.

2. Evaluate and treat any primary or secondary infectious complication. Patients with skin barrier dysfunction or skin failure often develop secondary bacterial infection, bacteremia, and sepsis. Patients should be cultured regularly, including any open areas of the skin in addition to standard infectious workup. Empiric antibiotics are often indicated in cases of skin failure.

3. Extensive history and detailed physical exam. Look for clues to specific diagnoses as noted above, which may direct therapy.

4. Stop any suspect medications that may be implicated in causing the cutaneous manifestations. Particularly in cases of SJS/TEN, cessation of the causative agent within 24 hours is associated with decreased mortality.

5. Early nutritional support is important in cases of widespread skin failure to allow healing and re-epithelialization.

6. Dermatological consultation is essential in the management of patients in the ICU with diffuse skin rash. Skin biopsy may be helpful in determining the underlying cause, and careful skin assessment by skilled dermatologists can aid in the diagnosis and management of critically ill patients with widespread skin rashes.

7. Reassess the patient regularly for signs of progression.

2. Emergency Management

Initial management of patients admitted to the ICU with diffuse skin rashes is complicated and depends somewhat on the extent and morphology of the skin rash.

1. Assess airway, breathing, and circulation. In cases of widespread skin failure and epidermal loss, severe cases may involve the upper airway and bronchi. Cases of widespread erythroderma and cutaneous vasodilatation may lead to circulatory collapse due to high-output cardiac failure. Patients with skin failure and widespread blistering may suffer massive insensible losses and develop hypotension and shock physiology. Patients with abnormal skin barrier function may develop bacterial infection and sepsis.

2. Obtain appropriate antimicrobial cultures and initiate empiric antibiotics unless contraindicated. Generally this should include agents covering skin flora, particularly staph and strep (depending on the clinical scenario, coverage for antibiotic-resistant strains may be indicated). Blood cultures and skin cultures are often necessary.

3. Consult dermatology. Certain entities require rapid diagnosis, and in some cases a STAT skin biopsy may be performed and frozen sections can be examined within minutes of arrival in the ICU. A trained dermatologist can help distinguish between many of the entities discussed in this section, and narrowing the differential diagnosis can tailor therapy and improve outcomes.

4. Monitor the patient for ongoing water and heat loss. In cases of widespread desquamation patients should be kept moist, with bland Vaseline, and have non-stick dressings applied to open areas. Nursing staff should be instructed to avoid tape-to-skin, and instead use gauze wraps and tape-to-gauze to prevent traumatization of the fragile skin, which may lead to further damage. In some cases, topical antimicrobial agents or topical steroids may be indicated. Often low- to mid- potency topical steroids and wet wraps will lead to improved comfort and more rapid resolution of a widespread eruption.

5. If the mucosa are affected, ophthalmology should evaluate the eyes, as patients with SJS/TEN frequently develop ocular scarring. The urethra should be monitored, and if involved, urological consultation is indicated

6. Perform a thorough history and physical exam to identify clues that may limit the differential diagnosis of widespread rash and point to more specific entities.

1. Thorough history and detailed physical exam including all mucosal surfaces

2. Fluid, electroylte, and nutrition replacement and temperature control

3. Cultures and antibiotics when indicated

4. Dermatology consultation with or without skin biopsy

5. Discontinue unnecessary and potentially inciting medications.

6. Careful skin care with clean or sterile handling, moisturization (with Vaseline or topical antimicrobials or topical steroids if indicated) and non-stick dressings

As diffuse skin rash in the ICU can result from a huge variety of different causes, a detailed description of the management of each is beyond the scope of this section. The essential component in the management of patients with widespread skin rash is to determine the underlying trigger, and focus treatment on that cause, while supporting the patient.

SJS/TEN requires special discussion as the management is complicated (for example, Fromowitz et al. have a set of University of Florida management guidelines with 28 steps). Offending agents that could be responsible for the reaction should be stopped, as should potential cross-reacting medications. Patients should not receive any non-essential medications. It is essential to rule out infection as a potential trigger (as HSV and mycoplasma, particularly in children, have been associated with SJS), and treat any primary or subsequent secondary infection. Some advocate for serial sampling of the skin to evaluate for colonization and monitor for antibiotic sensitivities. While controversial, more and more inpatient dermatologists are advocating early use of intravenous immunoglobulin, barring contraindications (absolute contraindications are IgA deficiency; relative contraindications may include a hyperviscous state, renal failure, or history of strokes). IVIg, when dosed appropriately (1g/kg/d daily for 3-5 days), may reduce mortality when compared to predicted SCORTEN mortality in some cases.

However, large-scale, randomized, controlled trials are lacking. Some physicians still advocate for corticosteroid use; this is controversial, and if used, steroids should be used early on in the disease course and tapered rapidly, as corticosteroids may delay wound healing and contribute to secondary infections. Fluid and electrolyte management, temperature control, and early nutritional support are essential, and pain control may be difficult – patient-controlled analgesia may be required. Ophthalmology should evaluate all patients with SJS/TEN regularly; if there is upper aerodigestive tract involvement, ENT should be consulted, and in cases of urethral disease, urology or gynecology should evaluate the patient.

Physical therapy is important in maintaining strength and preventing contractures. All areas of open, desquamating, denuded skin should be kept moist with either plain white petrolatum or, in some cases, 0.5% silver nitrate-impregnated wraps. Silver sulfadiazine should be avoided as sulfa drugs may precipitate SJS/TEN, and when applied over large areas silver sulfadiazine can induce neutropenia. The skin should be carefully preserved, with limited tape-to-skin and as few electrodes applied as required. Some authors advocate for therapeutic anticoagulation with heparin due to observed increased clot risks in these patients; it may be more appropriate to monitor patients closely and use low doses of prophylactic subcutaneous heparin to prevent DVT. Patients should be monitored closely, in the ICU or a burn unit, and ideally with dermatological consultation.

Patients must always avoid any drug triggers that could have caused SJS/TEN, and their first-degree relatives should also be counseled about potential heritable risk for severe drug allergy.

3. Diagnosis

To arrive at the correct diagnosis, patients should be evaluated by a skilled dermatologist as early as possible. While a thorough history and detailed physical examination may provide clues, particularly through analysis of the lesion morphology, past patient history, and timing of the eruption, a dermatologist may be invaluable in narrowing the differential diagnosis and directing the workup. A skin biopsy can provide useful information, and should be interpreted by a pathologist familiar with cutaneous disease. For certain diagnoses, laboratory evaluation may provide useful clues (patients with RMSF often have hyponatremia, while eosinophilia or atypical lymphocytes are part of the diagnostic criteria for DRESS, for example), as detailed above.

Pathophysiology

As this section reviews the wide array of potential causes of diffuse skin eruptions in patients in the ICU, diseases of multiple etiologies due to a wide variety of pathogeneses have been discussed. In general, in cases of widespread skin eruption, there is diffuse inflammation of the dermis or epidermis, which often leads to peripheral vasodilation of the skin and can cause high-output cardiac failure. Two key functions of the skin are to serve as an impermeable barrier, preventing water loss and preventing bacterial entry into the host.

Patients with widespread skin disease often lose fluid through their skin and develop profound electrolyte abnormalities. Bacteria may colonize diseased skin, and in cases of skin damage pathogens may enter the bloodstream and cause disseminated infection. The skin may also reflect systemic disease, with rashes resulting from immunologic abnormalities or septic/embolic seeding. In cases of diffuse proliferative abnormalities of the skin, rapid keratinocyte turnover may be a catabolic state requiring increased energy expenditure, and in cases such as this, as well as in cases of widespread skin loss requiring re-epithelialization, nutrition demands may be increased.

Epidemiology

This chapter discusses an array of diseases. In general, there is a trend towards more drug reactions in patients with HIV, lupus, or organ transplant, and in the elderly and in women more than men, presumably because these groups often take more medications. Patients with HIV are at a particularly elevated risk of severe adverse drug reactions. The most common cause of erythroderma is an exacerbation of an underlying skin condition, and patients with primary skin disease are at risk for progression to severe flares.

Special considerations for nursing and allied health professionals.

See sections above on care of patients with widespread skin rash: careful hand washing, aseptic/sterile technique, avoid increased skin trauma, place IVs as areas of normal skin, keep the patient clean, keep areas of skin loss/denuded skin moist and covered with non-stick dressings, monitor temperature, regular skin exams for progression.

What's the evidence?

Rothe, MJ, Bernstein, ML, Grant-Kels, JM. “Life-threatening erythroderma: diagnosing and treating the "red man."”. Clin Dermatol. vol. 23. 2005. pp. 206-217.

Ramos-e-Silva, M, Pereira, ALC. “Life-threatening eruptions due to infectious agents”. Clin Dermatol. vol. 23. 2005. pp. 148-156.

Bachot, N, Roujeau, JC. “Differential diagnosis of severe cutaneous drug eruptions”. Am J Clin Dermatol. vol. 4. 2003. pp. 561-572.

Hughey, LC. “Fever and erythema in the emergency room”. Semin Cutan Med Surg. vol. 26. 2007. pp. 133-138.

Seghal, VN, Srivastava, G, Sardana, K. “Erythroderma/exfoliative dermatitis: a synopsis”. Int J Dermatol. vol. 43. 2004. pp. 39-47.

Rothe, MJ, Bialy, TL, Grant-Kels, JM. “Erythroderma”. Dermatol Clin. vol. 18. 2000. pp. 1-16.

Vargas-Diez, E, Garcia-Diez, A, Marin, A, Fernandez-Herrera, J. “Life-threatening graft-vs-host disease”. Clin Dermatol. vol. 23. 2005. pp. 285-300.

Fischer, M, William, T, Wohlrab, J. “Skin diseases in intensive care medicine”. JDDG. vol. 7. 2009. pp. 108-115.

Sullivan, JR, Shear, NH. “Drug eruptions and other adverse drug effects in aged skin”. Clin Geriatric Med. vol. 18. 2002. pp. 21-41.

Kroshinsky, D, Grossman, ME, Fox, LP. “Approach to the patient with presumed cellulitis”. Semin Cut Med Surg. vol. 26. 2007. pp. 168-178.

Murray, RJ. “Recognition and management of toxin-mediated disease”. Int Med J. vol. 35. 2005. pp. S106-119.

Usatine, RP, Sandy, N. “Dermatologic emergencies”. Am Fam Physician. vol. 82. 2010. pp. 773-780.

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