Life-Threatening Skin Rashes

Necrotizing fasciitis is a bacterial infection most often localized to an extremity and is due to the extremely rapid penetration of the infection into the deeper tissues and the bloodstream.

The rash is a nonspecific term that refers to any visible inflammation of the skin. Most rashes are not dangerous and are self-limited. Life-threatening skin rashes are rare, but when they do occur, medical assistance is absolutely necessary.

Potentially life-threatening disorders that have a skin rash as a primary sign are

1. Pemphigus Vulgaris (PV),
2. toxic epidermal necrolysis (TEN), also known as Stevens-Johnson syndrome (SJS) or erythema multiforme major (EM),
3. drug rash with eosinophilia and systemic symptoms (DRESS) syndrome,
4. toxic shock syndrome (TSS),
5. meningococcemia,
6. Rocky Mountain spotted fever, and
7. necrotizing fasciitis.

These conditions produce a rash that may involve large portions of the skin surface. Usually, there are a variety of other significant symptoms and signs that accompany the rash and help to distinguish the cause.

Pemphigus vulgaris is an autoimmune skin disease that occurs when the body's immune system is misdirected and produces antibodies directed at a protein vital to the connection of epidermal cells. Toxic epidermal necrolysis and DRESS syndrome are hypersensitivity reactions, most often to drugs. Meningococcemia, Rocky Mountain spotted fever, and necrotizing fasciitis are due to an infection.

• Pemphigus vulgaris (PV)
  • PV is a disorder of the immune system (an autoimmune disorder). As in all autoimmune disorders, the body's natural immune system mistakenly identifies proteins within the skin as foreign by producing antibodies to attack the foreign intruder.
  • In PV, the target of these antibodies is a protein named desmoglein 3, which is part of a structure called a desmosome. Desmosomes are responsible for holding epidermal cells together.
  • Certain medications have been linked with the development of PV, including D-penicillamine (Cuprimine, Depen), captopril (Capoten), enalapril (Vasotec), penicillin, interleukin 2, nifedipine (Adalat CC, Procardia, Procardia XL), and rifampicin (Rifadin).
• Toxic epidermal necrolysis (TEN)
  • The exact cause of TEN is unknown, but it is thought to be a severe form of allergic reaction to certain medications or infections.
  • Antibiotics, typically sulfa-containing and penicillin-containing antibiotics, and medications given for seizures (phenytoin [Dilantin, Dilantin Infatabs, Dilantin Kapseals, Dilantin-125, Phenytek, Phenytoin Sodium, Prompt], phenobarbital [Solfoton], carbamazepine [Carbatrol, Equetro, Tegretol, Tegretol XR], and lamotrigine [Lamictal]) have been linked to TEN, as have the nonsteroidal anti-inflammatory drugs.
  • Other possible causes include viral infections with hepatitis, herpes simplex, Epstein-Barr, cytomegalovirus, and influenza viruses; bacterial infections with streptococcal-type and tuberculous bacteria; vaccination, particularly with the smallpox vaccination; and cancers.
  • Medications used to treat HIV, which include the protease inhibitors (PI) (atazanavir), the nucleoside reverse transcriptase inhibitors (NRTI) (efavirenz [Sustiva]), and the nonnucleoside reverse transcriptase inhibitors (NNRTI) (abacavir [Ziagen], nevirapine [Viramune]) have been associated with TEN.
• DRESS syndrome is an acronym for drug rash with eosinophilia and systemic symptoms.
  • This is a severe form of drug eruption that can begin two to six weeks after starting to take the offending drug. Frequent causes are anticonvulsants, namely phenytoin, phenobarbitone, carbamazepine, and lamotrigine. Other drugs incriminated include dapsone, sulphonamides, allopurinol, minocycline, terbina?ne, azathioprine, captopril, nevirapine, abacavir, and sulfasalazine.
• Toxic shock syndrome (TSS)
  • TSS is caused by an underlying infection with certain strains of Staphylococcus bacteria.
  • Bacterial toxins are released into the bloodstream, producing diffuse organ damage.
  • TSS became a public-health issue in the 1970s with the introduction of super-absorbent tampons. These tampons acted as a foreign body to support bacterial growth of the Staphylococcus bacteria.
  • Other infections that may lead to TSS include superficial skin infections, surgical wound infections, infections after delivering a baby, or infected nasal packings after nasal surgery or nosebleeds.
• Meningococcemia is a blood infection (septicemia) caused by Neisseria meningitis. This infection is most common in young adults and may also affect the membrane surrounding the brain and spinal cord. It is acquired through coughing, sneezing, or contaminated surfaces. Vaccination can prevent meningococcemia.
• Rocky Mountain spotted fever is an infection caused by a small microorganism called a Rickettsia and is transmitted to humans through the bite of a hard shell tick.
• Necrotizing fasciitis is a bacterial infection most often localized to an extremity and is due to the extremely rapid penetration of the infection into the deeper tissues and the bloodstream.

• Pemphigus vulgaris (PV)
  • PV happens more commonly in adults 40-60 years of age, but it has been found in children as young as 3 years of age and in adults as old as 89 years of age.
  • PV affects both women and men equally.
  • The painful blisters found in PV are irregularly shaped, elevated skin lesions, usually more than ½ inch across.
  • The blisters can form on either normal skin.
  • Lesions usually start in the mouth and may be found on the lips, tongue, throat, and the inside of the cheeks.
  • Painful blisters in the mouth make drinking and eating difficult.
  • Blisters then spread to the head, face, and armpits before moving on to the rest of the body.
  • As they form, blisters are initially tense and filled with clear fluid.
  • If you press on the skin next to a blister, the blister will either extend or a new blister will form.
  • After two to three days, the blisters become loose, and the fluid within the blister becomes cloudy.
  • At this stage, the blisters break easily, leaving a very painful area of raw skin underneath that quickly crusts over.
  • These open sores are very susceptible to infection.
  • Because the blisters can cover a large portion of the body surface, infection can be severe and easily spread into the blood.
  • If not treated, these severe infections may lead to death.
• Toxic epidermal necrolysis (TEN)
  • TEN occurs in all age groups but is more common among people 20-40 years of age.
  • TEN affects men twice as often as women.
  • The early symptoms include fever, muscle and joint pains, generalized fatigue, and itching or burning sensations in the skin.
  • The TEN rash starts in the mucous membranes, usually of the mouth and eyes, and may involve other mucous membranes in severe cases.
  • Then the skin lesions common to TEN develop. These lesions are often called "target lesions" because they have a white, bluish, or purple center surrounded by a circle of red.
  • These lesions start as reddened spots about 1 inch around and usually appear in clusters.
  • Although the rash may start anywhere on the body, it typically involves the feet, hands, and the front of the legs and arms more frequently than the chest, abdomen, or back.
  • The rash usually occurs on both sides of the body.
  • Blisters then form in the centers of the lesions and may itch or be painful.
  • Target lesions usually appear in successive crops over the body and coalesce, forming plaques affecting large portions of the skin.
  • The appearance can be quite like a "burn."

• Toxic shock syndrome (TSS)
  • TSS occurs in teens to young adults 15-34 years of age.
  • Two-thirds of people with TSS are younger than 25 years of age.
  • Four out of five are female.
  • Symptoms begin up to two days before the onset of skin rash and include fever greater than 102 F, sore throat, headache, fatigue, nausea, vomiting, and diarrhea.
  • TSS may involve the mucous membranes with red, irritated eyes, and a beefy-red tongue.
  • Dizziness or a lightheaded feeling when standing up is also common.
  • Joints and eyelids also may swell.
  • A diffuse red rash then rapidly appears that may cover most or all of the body.
  • If you press on the red areas of skin, the skin will blanch, or turn white. Releasing pressure will cause the redness to return.
  • The skin remains flat with no raised areas, bumps, or blisters.
  • Other organ systems also are affected by TSS, and TSS may lead to kidney, liver, respiratory, and heart failure. The brain may also be involved leading to confusion or disorientation.
  • Shock occurs when the cardiovascular system is unable to maintain blood pressure, leading to dizziness or lightheadedness when standing.
  • The rash will usually disappear in about three to five days.
  • During recovery, after the rash is gone, skin on the palms of the hands and soles of the feet begins to flake and peel off. In severe cases, fingernails, toenails, and hair may fall out. Other areas of skin may also begin to flake and peel.
• Meningococcemia
  • Within two weeks of exposure, patients become acutely ill with fever, low blood pressure, multiple organ failure, and a purple non-blanchable (unaffected by manual pressure) rash (purpura) often affecting the extremities. The rash represents blood that has leaked out of small vessels in the skin.
• Rocky Mountain spotted fever
  • Usually, there is fever and headache, severe muscle aches, and headache three to 12 days after the bite of an infected tick. A rash, which usually begins on the extremities and progresses to involve the torso, develops in a majority those affected within two to four days after the onset of fever.
  • The rash appears as pink bumps, but within a few days, many pinpoint reddish dots appear from blood leakage from capillaries in the skin.
• Necrotizing fasciitis
  • Necrotizing fasciitis is an infection that begins at a site of trivial or even unapparent trauma or in an operative incision. The initial lesion may appear only as an area of mild erythema but undergoes a rapid evolution over the next 24-72 hours. The inflammation becomes more pronounced and extensive, the skin becomes dusky and then purplish, and bullae containing yellow or hemorrhagic fluid appear. There is severe pain associated with fever. This can require aggressive interventions, including surgical operations.

Necrotizing fasciitis is a bacterial infection most often localized to an extremity and is due to the extremely rapid penetration of the infection into the deeper tissues and the bloodstream.

You must recognize these life-threatening skin rashes early to get the proper attention quickly. Contact the doctor if your symptoms include any of the following:

• Rash
  • Any rash that is sudden in onset and covers a large part of the body
  • Any rash that occurs shortly after starting a new medication
  • Any rash associated with a severe febrile flu-like illness
• Mouth sores: Any mouth sores that make it difficult to drink clear liquids
• Red eyes: Any sudden onset of red, inflamed eyes, accompanied by a rash or other illness
• Dizziness or lightheadedness when standing

You should go to a hospital's emergency department if you have any of the following symptoms or signs:

• Rashes that begin to blister over large portions of the body surface or when large portions of skin begin to peel
• Rashes that are purple to red, that appear bruise-like, and are associated with a febrile illness
• Fainting, or passing out
• Any mouth sores that are too painful to drink even small sips of liquids

Several of these disorders are difficult to diagnose in the emergency department. Blood tests, skin biopsies, and clinical presentation all play a factor in diagnosing each disorder. Doctors usually start treatment based on the symptoms and suspicion of one of these disorders and may not make a final diagnosis until after tests are done.

• A skin biopsy is taken using a special instrument designed to "punch out" a small round sample of skin.
  • Biopsy specimens are taken out of either normal skin near the rash or in an area of redness that has not yet blistered.
  • If skin biopsies are taken out of blistered areas, they are usually taken only from the skin forming the roof of the blister.
• Blood tests are sent for analysis to check for specific antibodies made by the body's natural immune system.
• Pemphigus vulgaris
  • Skin biopsy samples of the blistering skin and normal appearing skin next to blistering areas are tested.
  • Samples are stained to detect the antibodies that have attacked the proteins that hold together the outer layers of skin.
• Toxic epidermal necrolysis
  • Diagnosis is usually made based on symptoms of the rash typical to TEN, mucous membrane involvement, and use of medications that have been known to cause this disease. A history of having taken medications associated with SJS is not essential for the diagnosis. A history of a recent viral infection can be helpful in making the diagnosis. In some individuals, however, no cause for the development of TEN is found, resulting in a number of patients for whom the cause is without an identifiable cause (termed idiopathic).
  • Skin biopsy may also make diagnosis easier.
  • TEN is thought to be a more severe form of SJS.
  • Diagnosis is made based on signs and symptoms of a rash typical to TEN, mucous membrane involvement, and use of medications known to cause this disease. Like SJS, a history of having taken medications associated with TEN is not essential for the diagnosis.
  • Skin biopsy results show that the entire outer layer of skin has separated from the rest of the skin.
• Toxic shock syndrome
  • Diagnosis of TSS is based on the following symptoms: fever greater than 102 F, a diffuse red rash, systolic blood pressure less than 90 or fainting upon standing, and no evidence of other disease that may be causing the symptoms.
  • A TSS diagnosis also requires the involvement of three or more other organ systems as evidenced by the following:
    • Vomiting or diarrhea
    • Muscle pain or blood test that shows enzyme levels consistent with breakdown of muscle
    • Inflammation of the mouth, throat, vagina, or eyes
    • Blood test showing evidence of kidney or liver dysfunction
    • Disorientation or confusion
    • Heart failure
    • Respiratory failure
• Meningococcemia
  • Diagnosis is based on clinical findings and the identification of the organism from the blood or spinal fluid in a severely ill patient. The diagnosis must be suspected early and appropriate antibiotic therapy instituted before systemic organ failure becomes irreversible. In modern medical centers, the fatality rate is 10%-14%.
• Rocky Mountain spotted fever
  • The diagnosis is based on the clinical picture in a patient with a documented or suspected tick bite. Although identification of the organism is very important, treatment should be instituted early to avoid severe postinfection effects, as well as death. The disease is usually confirmed by a blood test.
• Necrotizing fasciitis
  • The diagnosis is suspected in a patient with acute onset of a severe febrile illness associated with an extremely painful infected extremity. X-rays examination of the affected extremity may be helpful. Diagnosis is confirmed by growing the bacteria isolated from the infected site or from the blood.

Because all of these disorders are life-threatening, home care is limited. Seeing the signs and symptoms early and going to a doctor right away are the only acceptable actions. If left without treatment, many of the people with any of these disorders may die. While getting to the doctor, the following care for symptoms can be started:

• Blisters
  • Do not break blisters that are intact.
  • As blisters break, do not attempt to peel away loose skin.
  • Cover blisters with sterile gauze or clean sheets.
  • Do not apply ointments or creams to blistered or raw skin.
• Fever
  • You may give acetaminophen (Tylenol) to control fever and help with some of the pain and discomfort. Ibuprofen (Advil) and naproxen (Aleve) (which are nonsteroidal anti-inflammatory drugs, or NSAIDs) should be avoided because of their association with the development of SJS and TEN.
  • Do not attempt to bring fever down with cold-water soaks or baths. This makes the person shiver and may actually increase internal temperature.
  • If the fever is severe, you may use towels soaked in lukewarm water to wipe down the parts of the body that are not blistered.
• Red eyes
  • Do not attempt to treat any rash that affects the eyes without seeking medical attention.
  • Do not use drops of any kind.
• Mouth ulcers or sores
  • Do not use mouthwash or any oral rinses to treat mouth sores at home.
  • Dehydration can occur if mouth sores are severe and pain limits the intake of fluids.
  • Frequent small sips of water or any sports drink should be encouraged to prevent or at least limit dehydration.

Treatment for all of these disorders involves a hospital stay.

• Admission to the hospital is the rule, and you may require admission to an intensive-care unit for closer monitoring.
• Blistering that involves large portions of the body is treated as a thermal burn. This can mean admission to a specialized intensive-care burn unit. Not all hospitals have a burn unit, so you may need to be transported to an appropriate medical center for care.
• The fluid losses through the skin and from decreased drinking that happen in these disorders cause dehydration.
  • This dehydration is treated with IV fluids.
  • One or two IV catheters will be placed in a vein, usually in the arms, for fluids and medicines as needed.
• Blood samples will be analyzed for signs of infection and electrolyte imbalances. IV fluids and electrolytes will be adjusted to normalize any electrolyte imbalance.
• Pemphigus vulgaris
  • Doctors try to suppress the body's immune system (to stop it from attacking itself) and stop the progression of PV with IV corticosteroids.
  • Blisters are treated like thermal burns and are very susceptible to infection. Antibiotic creams and sterile bandages that are changed frequently are used to prevent infection.
  • When blistered areas become infected, IV antibiotics are used, but they are not used to prevent infection.
  • Oral blisters are treated with mouthwashes and rinses with numbing medicine for pain relief.
• Toxic epidermal necrolysis
  • Doctors try to suppress the body's immune system (to stop it from attacking itself) and stop the progression.
  • Drying solution, such as Burow's solution, and sterile bandages are applied.
  • When blistered areas become infected, IV antibiotics are used, but they are not used to prevent infection.
  • Oral blisters are treated with mouthwashes and rinses with numbing medicine for pain relief.
  • An eye specialist monitors eye involvement. He or she may prescribe steroid and antibiotic eyedrops or ointments to be given while you are in the hospital.
  • Discontinue any medications that may be causing the disease.
  • Treatment of TEN must always be in an intensive-care unit or specialized intensive-care burn unit.
  • Using IV corticosteroids has not proven to help TEN, so they are not routinely used.
  • Raw areas of skin are covered with petrolatum gauze and sterile bandages that are changed frequently to help keep further fluid losses from happening through the skin.
  • When blistered areas become infected, IV antibiotics are used, but they are not used to prevent infection.
  • Oral blisters are treated with mouthwashes and rinses with numbing medicine for pain relief.
  • An eye specialist monitors eye involvement. He or she may prescribe steroid and antibiotic eyedrops or ointments to be given while you are in the hospital.
  • Discontinue any medications that may be causing the disease.
• Toxic shock syndrome
  • Large amounts of IV fluids may be required to treat the low blood pressure found in TSS.
  • Special medications may also be given continuously through an IV catheter to help increase blood pressure if fluids alone cannot raise blood pressure to adequate levels.
  • IV antibiotics are given immediately if TSS is suspected.
  • The underlying source of infection (that is, the tampon, nasal packing, wound infection, or other source) must be identified and removed.
• Meningococcemia
  • Treatment with the appropriate antibiotic is of major importance. If there is evidence of extensive tissue necrosis of the purplish extremity, then surgical treatment may be necessary.
• Rocky Mountain spotted fever
  • Treatment with doxycycline is usually begun prior to the confirmation of the diagnosis. The rash requires no specific treatment and will resolve along with the disease.
• Necrotizing fasciitis
  • If this diagnosis is suspected, an immediate surgical consultation is necessary to remove devitalized infected skin, fat, and muscle.

Each case and each disorder will need different follow-up care. The doctor responsible for your care while in the hospital will decide what sort of follow-up is best for you.

• Wound care: Many of the skin lesions will likely be healed or well on their way to healing by the time you are discharged from the hospital. Keep all healing wounds clean and dry. Use any medications or ointments only as prescribed by the doctor.
• Antibiotics: Antibiotics may be prescribed when you leave the hospital. Take all antibiotics as prescribed, until they are gone. Do not stop taking antibiotics, even if you are feeling better.
• Toxic shock syndrome: Some of these disorders may require long-term steroid pills. Others may only require steroids for a few days or weeks. The doctor may also prescribe a steroid taper -- that is, gradually decreasing the amount of steroids you are taking over time, until you are off them completely. Take all steroids exactly as the doctor prescribes. Stopping them suddenly can cause serious side effects and may lead to rehospitalization.

Prevention is often difficult, because few clear causes have been found for any of these diseases. A few general guidelines are suggested.

• Do not try to avoid every medicine thought to be associated with any of these disorders. Serious medication allergies are extremely rare. Simply avoid taking medications to which you have a known allergy. Always alert your doctor to potential medication allergies you may have.
• Many of the infections thought to cause these disorders are almost impossible to avoid and are virtually always harmless infections.
• Avoiding tampons can help prevent TSS. The super-absorbent tampons introduced to the market in the 1970s are no longer available in the U.S., and tampons now in the marketplace are considered safe. When using any tampons, however, change them frequently.
• Meningococcemia is prevented with a vaccination. It is recommended that individuals at high risk for exposure, incoming college freshman living in dormitory environments, and those traveling to endemic areas be vaccinated.
• Rocky Mountain spotted fever can be prevented to a great extent by careful inspection for ticks after hiking in endemic areas. Wearing tick-repellent clothing can be very helpful. Ticks can be removed with a fine tweezer ASAP.

These disorders pose a serious risk for death if they do not get treated. Early treatment and care in a hospital or intensive-care unit greatly increases the chance of survival.

• Pemphigus vulgaris: Despite early treatment, some people with PV will die. Delay in starting treatment makes death more likely. Many people require long-term steroid use to control the disease.
• Stevens-Johnson syndrome: Those with SJS who receive treatment have a high chance of survival.
• Toxic epidermal necrolysis: Even with treatment, a large percent of people with TEN have a very poor outlook and may die.
• Toxic shock syndrome: With medical treatment, most people will recover.
• The outlook for Rocky Mountain spotted fever currently is a 5%-10% fatality rate.
• Meningococcemia has a 10%-14% fatality rate.
• Necrotizing fasciitis can have a fatality rate as high as 7%-12% in modern medical settings and leave patients with significantly deformed extremities.