Treatment of severely ill dermatologic patients presented with : Erythroderma Steven Jonson syndrome Toxic Epidermolysis Necrosis

1- Erythroderma Exfoliative dermatitis (ED) is a definitive term that refers to a scaling erythematous dermatitis involving 90% or more of the cutaneous surface. Exfoliative dermatitis is characterized by erythema and scaling involving the skin's surface and often obscures the primary lesions that are important clues to understanding the evolution of the disease.

Etiology Frequently the result of the generalization of an underlying dermatosis : Psoriasis , Atopic dermatitis , chronic actinic dermatitis. Seborrheic dermatitis , Pityriasis rubra pilaris , Allergic contact dermatitis Drug eruptions Idiopathic Malignancy: Cutaneous T-cell lymphoma Paraneoplastic erythroderma

Drug eruptions : The most commonly implicated drugs include: • Anti-epileptics • Allopurinol • Antibiotics : Penicillin , Sulfonamides , Vancomycin. •Calcium channel blockers • Cimetidine • Dapsone • Gold • Lithium • Quinidine

How it is present : skin appears inflamed, edematous and scaly Systemically unwell with lymphadenopathy and malaise

Pathophysiology : An increased skin blood perfusion that results in temperature dysregulation and possible high-output cardiac failure. The basal metabolic rate rises to compensate for the resultant heat loss. Fluid loss by transpiration is increased in proportion to the basal metabolic rate. The situation is similar to that observed in patients following burns . Hypoalbuminemia results, in part, from decreased synthesis or increased metabolism of albumin. Edema is a frequent finding, probably resulting from fluid shift into the extracellular spaces.

1) Attention to nutrition, fluid and electrolyte replacement. Management : Initial approach to the management of erythroderma of any etiology includes: 1) Attention to nutrition, fluid and electrolyte replacement.  2) Institution of gentle local skin care measures.  3) Wet dressings to weeping or crusted sites should be followed by application of topical corticosteroids

Stevens-Johnson syndrome

What is Stevens-Johnson syndrome : Stevens-Johnson syndrome is a rare, serious disorder of your skin and mucous membranes. It's usually a reaction to a medication or an infection. Often, Stevens-Johnson syndrome begins with flu-like symptoms, followed by a painful red or purplish rash that spreads and blisters. Then the top layer of the affected skin dies and sheds. Stevens-Johnson syndrome is a medical emergency that usually requires hospitalization

The causes : Various etiologic factors have been implicated as causes of Stevens-Johnson syndrome. Drugs most commonly are blamed. The 4 etiologic categories are as follows: Infectious Drug-induced Malignancy-related Idiopathic: Stevens-Johnson syndrome is idiopathic in 25-50% of cases. Drugs and malignancies are most often implicated as the etiology in adults and elderly persons. Pediatric cases are related more often to infections.

Infectious causes: Viral diseases that have been reported to cause Stevens-Johnson syndrome include the following: Herpes simplex virus (possibly; remains a debated issue) AIDS Coxsackie viral infections Influenza Hepatitis Mumps In children, Epstein-Barr virus and enteroviruses have been identified as being associated with the development of Stevens-Johnson syndrome. More than half of the patients with Stevens-Johnson syndrome report a recent upper respiratory tract infection.

Bacterial infections: Group A beta-hemolytic streptococci Diphtheria Brucellosis Lymphogranuloma venereum Mycobacteria Mycoplasma pneumoniae  Rickettsial infections Tularemia Typhoid Possible fungal causes include coccidioidomycosis, dermatophytosis, and histoplasmosis. Malaria and trichomoniasis have been reported as protozoal causes.

Drug induce : Analgesics, cough and cold medication NSAIDs Antibiotics are the most common cause of Stevens-Johnson syndrome Analgesics, cough and cold medication NSAIDs Psycho-epileptics Antigout drugs

Genetic factors: There is strong evidence for a genetic predisposition to severe cutaneous adverse drug reactions such as Stevens-Johnson syndrome. Carriage of the following human leukocyte antigens has been associated with increased risk

Management : Early diagnosis and withdrawal of suspected drug(s). Patients are best cared for in an intermediate or intensive care unit. 
 Manage replacement of IV fluids and electrolytes as for patient with extensive thermal burn. Systemic glucocorticoids early in the disease and in high doses are reported helpful in reducing morbidity or mortality (as is also the experience of the authors), but this has been questioned. Late in the disease, they are contraindicated. High-dose IV immunoglobulins halt progression of TEN if administered early. 
 Diagnose and treat complicating infections, including sepsis (fever, hypotension, change in mental status). Treat eye lesions early with erythromycin ointment.

Toxic epidermolysis necrosis

What is toxic epidermal necrolysis (TEN) Toxic epidermal necrolysis (TEN) is a potentially life-threatening dermatologic disorder characterized by widespread erythema, necrosis, and bullous detachment of the epidermis and mucous membranes, resulting in exfoliation and possible sepsis and/or death (see the image below). Mucous membrane involvement can result in gastrointestinal hemorrhage, respiratory failure, ocular abnormalities, and genitourinary complications.

The pathophysiology : The pathophysiology of TEN has not been fully elucidated; however, various theories have received wide acceptance. TEN is believed to be an immune-related cytotoxic reaction aimed at destroying keratinocytes that express a foreign antigen. TEN mimics a hypersensitivity reaction, with its characteristic delayed reaction to an initial exposure and an increasingly rapid reaction with repeated exposure The widespread epidermolysis and blistering of TEN results from keratinocyte apoptosis—an organized series of biochemical reactions leading to cell changes and cell death.

Etiologies : Medications : Infections (e.g. Mycoplasma pneumonia) Sulfonamide antibiotics. Allopurinol. Amine antiepileptics. Phenytoin. Carbamazepine. Lamotrigine NSAIDs (72) Infections (e.g. Mycoplasma pneumonia) Other: Vaccinations, Systemic diseases, Chemical exposure, Herbal medicines, Foods

TEN= > 30% of skin involvement 10-30%= SJS/TEN overlap < 10% = Stevens-Johnson 20-30% mortality rate Incidence of 1-2 per million

SCORTEN Severity of illness score Probability of hospital mortality Similar past formula was age + TBSA

Variables Odds Ratio p-value Age (40  y old) 2.7 (1.0-7.5) 0.05 Heart Rate ( 120 bpm) 2.7 (1.0-7.3) 0.04 Cancer/hematologic malig. 4.4 (1.1-18.0) BSA involved at day 1 < 10% 1 10-30% 2.9 (0.9-8.8) > 30% 3.3 (1.2-9.6) Serum urea level ( >10mmol) 2.5 (0.9-7.3) 0.09 Serum bicarb (<20 mmol/L) 4.3 (1.1-16.0) 0.03 Serum glucose (>14mmol/L) 5.3 (1.5-18.2) <0.01 SCORTEN 2.45 (2.26-5.25) <10-4

Mortality Rates and Relative Risks SCORTEN # patients % mortality 95% CI Odds Ratio 0-1 31 3.2 (0.1-16.7) 1 2 66 12.1 (5.4-22.5) 4.1 3 34 35.3 (19.8-53.5) 14.6 4 24 58.3 (36.6-77.9) 42.0 5 10 90.0 (55.5-99.8) 270.0

Management : Prompt recognition of the disorder and withdrawal of all potential causative agents. Supportive care until the epithelium regenerates. Supportive measures include isolation, fluid and electrolyte balance, nutritional support, pain management, and protective dressings. Early transfer of patients to a burn or intensive care unit has been shown to reduce the risk of infection, mortality rate, and length of hospitalization. No specific treatment modality has been proven effective, but agents such as crystalloids, antibiotics, antihistamines, anticoagulants, analgesics, and antiseptic agents are important for supportive care. Use of corticosteroids is controversial.

Sources: -Wiley online library http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2230.1982.tb02450.x/abstract -ScienceDirect http://www.sciencedirect.com/science/article/pii/S0738081X0400118X http://emedicine.medscape.com/article/229698-medication Dermatology hand book for medical students & junior doctors

Done by : Jude wael Fatimah barghawi Lujaina reda Afnan alotaibi Fatimah almuhana Duaa aleeli Aliaa alyousef Zahraa aljafil Hajar bangitah Amani alawaji