Identifying and Managing Rare Drug-Induced Dermatologic Emergencies

Introduction:

Dermatologic emergencies are commonly encountered in the emergency department of hospitals. The doctors find it quite challenging to address dermatologic emergencies, as the former overlaps with the underlying disease and co-morbid conditions from which the patient is already suffering, making the diagnosis and treatment planning difficult, which in turn greatly affects the prognosis. Adverse drug reactions can lead to life-threatening dermatologic emergencies. Hence, a detailed medical and personal history should be elicited, with a thorough physical examination to rule out the possibility of drug reactions that worsen the clinical condition.

What Are the Drug-Induced Dermatologic Emergencies Encountered in the Emergency Department?

1. Toxic Epidermal Necrolysis (T.E.N):

Etiology:

Toxic epidermal necrolysis (T.E.N) is a rare dermatological emergency, associated with higher mortality rates and is treated in an intensive care unit or burns unit.

T.E.N. is most commonly caused by adverse drug reactions. Patients suffering from T.E.N. are more prone to recurrence with repeated exposure to the offending drug. The patient’s family is more prone to getting exposed to T.E.N. It can also occur due to acute graft versus host disease, which usually turns out to be fatal.

The most common drugs responsible for T.E.N are the following.

• Allopurinol.

• Sulfonamides.

• Anticonvulsants like Phenytoin, Carbamazepine, Lamotrigine.

• Nonsteroidal anti-inflammatory drugs.

Pathophysiology:

The pathophysiological mechanism occurs when lymphocytes (immune cells) and cytokines cause cell-mediated cytotoxic reactions against the epidermal cells.

Clinical Features:

• Fever.

• Tender erythema involving mucosa involving more than 30 percent of the skin surface causes inflammation, pain, and ulceration.

• Respiratory failure in case of tracheal mucosal involvement.

• Denudation and full-thickness skin and mucosal necrosis.

• Prodromal rashes.

• Target lesions.

• Shedding of hair and nails.

• Anemia.

• Leukopenia (decreased white blood cell count).

• Hepatitis.

• Intense abdominal pain.

• Encephalopathy (permanent or temporary damage to the brain).

• Myocarditis (inflammation of the myocardium).

Diagnosis:

Underlying diseases and complications should be ruled out by performing specific investigations. Bacterial infections should be ruled out by taking skin swabs.

CBC (complete blood count) to detect anemia and neutropenia. Biochemistry tests to detect hypoalbuminemia (decreased albumin protein in the blood)and hyponatremia (decreased sodium level in the blood).

Skin biopsies should be carried out as they serve as an important diagnostic clue in detecting the following.

• Necrotic keratinocytes (damaged skin cells -which protect the skin against UV rays and other forms of skin damage).

• Subepidermal sloughing (loss of layer beneath the epidermis of skin).

• Mixed perivascular inflammatory infiltrate (mild form) (collection of acute and chronic inflammatory cells around a blood vessel wall).

Complications:

T.E.N has significantly higher morbidity and mortality rates, especially in cases of bacterial sepsis and in elderly patients, due to:

• Dehydration.

• Loss of protein.

• Failure to achieve thermoregulatory homeostasis.

• Renal tubular necrosis.

• Eroded gastrointestinal tract.

• Interstitial pneumonitis.

• Neutropenia (decreased number of neutrophils- a type of blood vessel).

• Heart and liver failure.

Differential Diagnosis:

• Erythema multiforme major, which affects <10 percent of the body surface area.

• Staphylococcal scalded skin syndrome.

• Scarlet fever.

• Toxic shock syndrome.

• Thermal burns.

• Acute graft versus host disease.

• Severe bullous drug eruption (side effects of certain drugs causing fluid-filled blisters on the skin).

• Drug hypersensitivity syndrome.

• Exfoliative dermatitis (erythroderma).

Management:

• The offending drug should be eliminated as soon as possible and should never be re-administered as it is associated with higher recurrence rates.

• The management of T.E.N should always be carried out in the ICU (intensive care unit).

• Supportive therapy includes placing the patient in a warm environment, fluid resuscitation as and when required, correction of electrolyte imbalance, administering high-calorie enteral intake, and prevention of sepsis.

• Analgesics are given to relieve the pain.

• IV (intravenous) administering antibiotics to prevent opportunistic bacterial infections.

• Mucosal emollients are advised to apply to the lesions to ease the discomfort.

• Prompt debridement of necrotic lesions.

• Non-stick occlusive burn dressings are given.

• Granulocyte colony-stimulating factor is administered to treat neutropenia.

• Intravenous immunoglobulins or Cyclosporin are given to stop the cytotoxic process against the epidermal cells.

• Systemic corticosteroids should be avoided.

• Recovery takes place from ten days to three weeks and is usually associated with irregular pigmentation and scarring of the mucosa.

2. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome:

Etiology:

Drug reaction with eosinophilia and systemic symptoms (DRESS's syndrome) is a rare disorder caused due to adverse drug reaction following the first exposure to an offending drug affecting the skin and other internal organs. Clinical manifestations occur after exposure with a latency period of two to three weeks.

Many drugs tend to precipitate DRESS, of which the most commonly associated ones are as follows:

• Carbamazepine, Phenytoin, Phenobarbital (aromatic antiepileptics).

• Lamotrigine.

• Trimethoprim-sulfamethoxazole (Sulfonamide antibiotics).

• Minocycline, Dapsone.

• Allopurinol (Xanthine oxidase inhibitors).

• Sulfasalazine (Aminosalicylates).

• Abacavir (Reverse transcriptase inhibitors).

• Gold salts (Antirheumatics).

Pathophysiology:

DRESS syndrome occurs when the detoxification mechanism of a drug is hampered, leading to the accumulation of harmful metabolites.

Reactivation of herpes viruses like HHV-6 and 7 (human herpes virus) also plays a major role.

Clinical Features:

• Characterized by a triad of fever, rash, and internal organ involvement.

• Central facial erythema (reddish discoloration of the skin caused due to increased blood supply).

• Edema (accumulation of fluid within the tissues).

• Generalized lymphadenopathy (generalized swelling of the lymph nodes).

• Leukocytosis (increased white blood cells).

• Abnormal liver function tests.

• Peripheral eosinophilia.

• The liver is the most commonly involved internal organ.

• Generalized cutaneous and visceral inflammations.

Diagnosis:

• Morphological variations of cutaneous eruptions and involvement of the internal organs pose quite challenges in arriving at the diagnosis.

• The diagnosis is made using the regiSCAR diagnostic criteria, which include hospitalization, presence of acute rash, and suspicion of a drug-related reaction.

• Fever, lymphadenopathy involving at least two regions, and involvement of internal organs like the liver, heart, and kidney give a clue.

• Laboratory investigations showing hematologic abnormalities, a high or low lymphocyte count, a high eosinophil count, and a low platelet count can aid in diagnosis.

Differential Diagnosis:

• Exfoliative dermatitis.

• Collagen vascular diseases.

• Atopic dermatitis.

• Eosinophilic pneumonia.

• Vasculitis (inflammation of the blood vessels).

• Hodgkin disease (cancer involving the lymphatics of the body’s immune system, making the body fight against the infection).

• Parasitic infections.

• Eosinophilic toxocariasis (a helminth infection causing increased count of eosinophils - a type of white blood cell.

• Allergic diseases.

• Angiolymphoid hyperplasia with eosinophilia (a benign proliferative disorder of blood vessels accompanied by increased eosinophil count).

Complications:

Complications may evolve after the regression of DRESS's syndrome owing to the impaired regulatory action of the T lymphocytes in the recovery phase, which include:

• Systemic lupus erythematosus (an autoimmune disease characterized by generalized inflammation involving the skin, joints, brain, kidneys, lungs, and blood vessels).

• Autoimmune hemolytic anemia.

• Reactive arthritis.

• Alopecia areata.

• Vitiligo (a disease which is associated with loss of skin color occurring in patches).

Management:

• Stopping the offending drug as soon as possible is the mainstay of the treatment plan.

• Systemic corticosteroids are prescribed after the offending drug withdrawal as the patient will be in an immuno-compromised state.

• Steroids are given in gradual tapering doses.

• Immunosuppressants like Cyclosporine are given for refractory cases.

• Substituting the aromatic anticonvulsant with a non-aromatic anticonvulsant is beneficial as the former precipitates the DRESS syndrome.

• Cross-reactivity between the two classes of drugs should be avoided as it can lead to greater recurrence rates.

Conclusion:

Many dermatological diseases present as potentially life-threatening emergencies, and the role of emergency physicians in recognizing the milder ones and the serious conditions plays an important role in providing immediate intervention for complex cases. The features of many dermatological conditions overlap with the underlying conditions and can sometimes mislead the diagnosis. Hence, interpersonal collaboration should be made by taking a dermatologic consultation for effective management, and meticulous wound care in such complex cases proves to be beneficial.