Acute skin failure

Acute skin failure in ICU

1. ACUTE SKIN FAILURE FADEL KAMAL, MD ICU REGISTRAR

2. Introduction The concept of an ICU in dermatology setting was first introduced in 1974 by Prof. Rene Touraine . Dermatological diseases accounts for 8%–20% of the patients visiting emergency outpatient department globally.

3. Introduction Acute Skin Failure refers to a state of tissue hypoperfusion that leads to tissue death. Although the skin accounts for 10% to 15% of the total body weight, it requires 25% to 33% of cardiac output, and thus, is the largest single organ of the human body.

4. Introduction In view of increased immunosuppressed state, availability of organ transplant, use of multiple drugs, malignancies, and indiscriminate use of drugs including homeopathic and ayurvedic , the possibility of a patient culminating into acute failure of skin has increased.

5. PATHOPHYSIOLOGY

6. Hemodynamics Persistent inflammation leads to; Peripheral vasodilatation Increased cutaneous blood flow . Edema . There is increased blood volume and cardiac output, which may jeopardize an already compromised cardiovascular system resulting in high-output cardiac failure.

7. Thermoregulation Hypothermia is a very common . Fever in the absence of infection mediated by interleukin-1, produced by damaged keratinocytes . Intraepidermal occlusion of the sweat ducts. Sudden onset hypothermia in a relatively stabilized patient, rather than fever, may be a premonitory sign of septic shock .

8. Metabolic Rise (BMR ). A hyperglycemic state & glycosuria are common in (50%) & result from associated pancreatitis and decreased insulin secretion, relative insulin resistance, stress. Altered glucose metabolism enhances caloric loss by depleting tissue protein as an energy source. Shivering as a compensatory mechanism for hypothermia, is also highly energy consuming

9. Fluids and electrolytes Impaired barrier function of the skin resulting in increased transepidermal water loss (TEWL), & enhanced percutaneous fluid loss by transpiration (proportionate to the raised BMR). The average daily fluid loss in adult TEN patients with approximately 50% body surface area (BSA) involvement is 3-4 liters .

10. Fluids and electrolytes Reduction in the intravascular volume and formation of hyperosmolar urine. This is associated with electrolyte imbalance ( low Na+ and high K+ ), and raised serum levels of urea and creatinine (prerenal uremia).

11. Fluids and electrolytes Patients with TEN & autoimmune bullous disorders have, in addition, extra loss of Na+, K+ and Cl - in the blister fluid, Hypophosphatemia is a common complication aggravating insulin resistance, & altering the neurological status & diaphragmatic function. Patients with acute generalized pustular psoriasis may develop acute hypocalcaemia secondary to severe hypoalbuminemia .

12. Destruction of stratum corneum , the layer mainly responsible for the barrier function of the skin, cause up to 40 times increase in fluid loss than the normal rate of 1 ml/cm2/hour , 50% (BSA) involvement leads to daily fluid loss of up to 4-5 liters . Fluids and electrolytes

13. Nutrition The main causes of hypoproteinemia are Continuous loss through shed scales. Increased BMR. Decreased hepatic synthesis. Dermatogenic enteropathy leading to protein loss. Dilution due to hypervolemia .

14. Nutrition The normal material exfoliated from the skin amounts to 500-1000 mg/day. It is increased several folds ( 9 g/m2 BSA/day) in different disease states precipitating ASF. Diffuse scaling leads to protein loss of approximately 20-30 g/m2 BSA/day . In presence of exudative skin lesions, the combined protein loss through oozing from the skin surface & urine may amount to 150-200 g/day.

15. Nutrition Loss of proteins (40 gm/L) , Na (120-150 mmol /L) , Cl (10-90 mmol /L) and K (5-10 mmol /L) in the bullous fluid leads to decrease in intravascular volume. The resultant decrease in urinary output and increased blood nitrogen can lead to renal failure unless treated energetically.

16. Nutrition The cumulative effect of these factors is a - Ve nitrogen balance, increased urinary nitrogen & hypoalbuminemia . Muscle wasting. In addition to the loss through the shed skin, there is impaired absorption of iron and vitamin B12 & folate deficiency, contributing to anemia.

17. Edema Peripheral edema 1. Increased capillary leakage 2. Hypoalbuminemia 3. Associated cardiac failure 4. Inflammation resulting from the primary skin disease VPF & VEGF are cytokines liberated by keratinocytes which induce dermal capillary proliferation and enhance micro vascular permeability.

18. Pulmonary Complications Severe pulmonary edema (2 ry to capillary leak syndrome) & ( ARDS ) are complications of erythroderma. Over correction of hypovolemia frequently gives rise to overt pulmonary edema (30%).

19. Immunity Lymphopenia , Neutropenia & Thrombocytopenia are well-known complications of TEN. Impaired chemotaxis & phagocytosis of granulocytes and low serum gamma globulin levels are common. CD4+ T- lymphocytopenia may be associated even in the absence of HIV infection.

20. Susceptible for infections Damaged skin and its exudates support growth of a wide spectrum of endogenous & exogenous organisms leading to systemic infection, severe sepsis and death.

21. Long Term Complications Eye : Ectropion, corneal scarring DVT , stress ulcers Mucosal involvements : Esophagus: Stricture, Dysphagia Urethra: Stricture, Synechiae Vagina: Stricture, Synechiae Skin: Pigmentry changes Hair: Scaring alopecia Nails: Dystrophy

22. Classification of skin disease

23. Common dermatoses leading to ASF Clinical spectrum of Erythema multiform ranges from mild (EM minor) to severe (SJS , complex and TEN). Severe drug reactions. Bullous diseases . Burn.

24. Erythema multiform Acute, self-limiting , mucocutaneous reaction pattern to many viral, bacterial, protozoa & fungal infections, tumors, drugs, autoimmune states and miscellaneous conditions. HSV infection is the most frequent cause followed by mycoplasma pneumoniae .

25. Erythema multiform Consists of symmetrically distributed polymorphic rash classically with iris or target lesions seen on hands with a central vesicle, or erythema surrounded by a pale and then a red ring. Clinical spectrum of Erythema multiform ranges from mild (EM minor) to severe (SJS , complex &TEN).

26. Severe Drug Reactions Types

27. Severe Drug Reactions Signs

28. Severe Drug Reactions Culprits

29. Morbilliform rash with fever and internal organ involvement “Toxic erythema” Mortality - about 10% Later onset (2-6 weeks) after new drug commenced Fever, lymphadenopathy Eosinophilia Hepatic / renal failure Treatment: withdrawal of offending drug(s) and supportive care DHS - clinical features

30. DHS - CULPRITS

31. Drug Induced Urtecaria

32. Drug Induced Urtecaria Culprits

33. Bullous diseases Immunobullous diseases like pemphigus, pemphigoid, etc. and hereditary mechanobullous disorders like epidermolysis bullosa can be disabling and even life-threatening in some cases.

34. Pemphigus vulgaris: There are three main types of pemphigus- P foliaceous , (the blister is in the superficial granular layers), P vulgaris , (the blisters form just above the basal layer) & paraneoplastic pemphigus that occurs in association with malignancy. Bullous diseases

35. Though flaccid blisters are the primary lesions of pemphigus, erosions are common and usually painful. Nikolsky’s sign is positive . Bullous diseases

36. Bullous pemphigoid: This subepidermal blistering skin disease of the elderly is characterized by large, tense bullae arising on normal or erythematous skin.. Bullous diseases

37. Case Discussion

38. A 74-year-old male patient visited Dongguk University Gyeongju Hospital with high fever and a drowsy mental state. He was admitted to the intensive care unit (ICU) because of septic shock due to bacterial pneumonia . His MAP dropped to 50–60 mmHg. Initial blood examination revealed the following : leukocytes, 38,740/ μL ; myoglobin , 7,896 ng / mL ; creatine kinase >3,000/ μL . The amount of urine was less than 300 mL /day . Hemodynamic instability occurred, and was attributed to acute respiratory failure and acute renal failure . After 2 weeks of treatment in the ICU, he began to regain health gradually, and his vital signs stabilized.

39. In the ICU, to prevent PU, position changes were performed every 2 hours, using an air mattress . Pressure on bony prominences was dispersed by using a donut-shaped pouch. Three days later, despite efforts to prevent PU, multiple skin ulcers had developed that were not present at admission. The lesions developed simultaneously and progressed rapidly . Of particular note, the lesion on the left buttock was not round , but was pear-shaped, unlike common PU.

40. Case Discussion Many authors contribute to confusion by interchangeably using terms that refer to unavoidable PU-like lesions, such as ASF, unavoidable PU, and Kennedy terminal ulcer. Because of the absence of clear diagnostic criteria, these terms are often used inappropriately.

41. Skin failure is defined as an event that causes the skin and underlying tissue to die due to hypoperfusion concurrent with severe dysfunction of another organ system. Case Discussion

42. The National Pressure Ulcer Advisory Panel defined unavoidable PU as an ulcer that forms because of an individual’s clinical conditions & risk factors , despite the proper application of standard preventative measures.

43. A Kennedy terminal ulcer is defined as unavoidable skin breakdown or skin failure associated with the dying process .

44. Why ASF not PU ? The multiple skin ulcers were caused by ischemia secondary to poor perfusion related to septic shock with multiorgan failure . Multiple skin ulcers occurred despite the implementation of proper preventative measures . The shapes and locations of the ulcers did not correspond with those of typical PU . Multiple skin ulcers occurred simultaneously and rapidly.

45. Diagnosis The diagnosis is primarily based on the appearance of the skin lesions and their typical symmetrical distribution , especially if known risk factors are present. Rule of nines Scortne score Nikolsky ’ s sign

46. Rule of Nines

47. SCORTEN score

48. The following investigations can be done in all patients Complete blood count . Serum electrolytes . Complete urine examination ( hematuria & proteinuria are indicative of renal involvement) . Blood sugars. Liver function tests (SGOT , SGPT are slightly elevated in half of the patients ; or due it frank hepatitis caused by drugs, sepsis or shock) . Renal function tests . Chest x ray . HIV . Skin Biopsy ( to confirm the diagnosis).

49. General Management

50. General Management  Promptly discontinue any and all possible offending drugs . Admit the patient in an ICU or burns ward . Assess the condition of the patient to determine the prognosis based on the SCORTEN score.

51. Fluid & electrolyte imbalance • The fluid requirement is calculated based on the parklands formula & 3/4ths of this total amount is given to a pt with TEN (Parkland’ formula = 4 ml/kg body wt × % BSA).

52. Fluid & electrolyte imbalance Isotonic saline 0.7ml/kg/% of BSA affected and human albumin 1ml/kg/% BSA. Potassium phosphate is added to I/V fluids to prevent insulin resistance. About 1500ml of nasogastric feed can be given in addition on first day.

53. Nutritional support Patient should be allowed to eat a soft diet . Then NGT feeding or parenteral feeding can be given Early and continuous feeding decreases the risk of stress ulcers, reduces bacterial dislocation, enterogenic infection. Golden guidance Indirect calorimetry.

54. Nutritional support Aggressive nutritional support to compensate the hypercatabolic state & to promote tissue healing. Energy requirement in adults is 1500- 2000 Kcal in first 24 hrs; with an increment of 500 Kcal daily up to 3500-4000 Kcal/day. Protein intake of 2-3 gms /kg/day (3-4 gms /kg in children) should help in faster healing.

55. Indirect Calorimetry

56. Temperature control Nursing in a room at temperature of 30-32°C , in an air-fluidized bed is helpful.

57. Wound care Detached or detachable epidermis should be left in position as a biological dressing & only the denuded skin be covered with a dressing. Petrolatum impregnated gauzes can be used.

58. Wound care Topical antiseptics like silver sulphadiazine (contraindicated in patients sensitive to sulpha drugs) should be applied after proper bath/soaks with potassium permanganate solution. Peripheral line is more recommendable than centra l, which has a higher chance of infection, but good peripheral venous access is difficult to find.

59. Wound care All lines should be checked for signs of infection daily and changed two times a week with tips of lines and catheters sent for culture. Care of mucous membranes like eyes, nose, mouth, genitals , etc., is essential to prevent morbidity and infections.

60. Ophthalmic care 2 hourly instillation of eye drops ( saline or antibiotic drops ) Apply ointments at night. Developing synechiae are disrupted by a blunt instrument. Systemic Abx. & Anti-fungal if suspected endophthalmitis.

61. Medical Management

62. CORTICOSTEROIDS Role of corticosteroids is controversial Systemic corticosteroids may delay wound healing , increase the risk of infection , mask early signs of sepsis , and may precipitate gastrointestinal bleeding . But if the involved area is more than 20% of BSA , then the advantages of treatment outweighs its drawbacks.

63. CORTICOSTEROIDS Give oral prednisolone (1-2 mg/kg/day) or parenteral steroids ( dexamethasone 8-16 mg daily or hydrocortisone ) can be started within the first 72 hours in a patient with limited skin surface involvement to prevent wide spread diffusion , and continue for 3-5 days followed by rapid tapering.

64. CYCLOSPORINE It acts by inhibiting the activated T lymphocytes , macrophages & also interferes with the metabolism of TNF-α and possesses anti apoptotic properties. Cyclosporine interrupts the disease progression & decreases the time taken for complete reepithelization.

65. CYCLOSPORINE Dose is 3-5 mg/kg/day oral or IV up to 2 weeks followed by weaning over another 2 weeks • Side effects are hypertension, renal toxicity ( but these effects are not seen with short duration of treatment). Watch out septic complications and severe leucopenia .

66. INTRAVENOUS IMMUNOGLOBULINS Can be considered if pt is seen within 48-72 hrs. of bulla onset & in cases with active progressing lesions even after 72 hrs. Total dose is 2 gm/kg , which is given as 0.4 g/kg/day for 5 consecutive days.

67. INTRAVENOUS IMMUNOGLOBULINS Adverse effects are risk of thromboembolism , hemolysis, vasomotor symptoms & anaphylactic reactions But the major limiting factor is its high cost.

68. DEXAMETHASONE- CYCLOPHOSPHAMIDE PULSE THERAPY Involves IV administration of 100 mg of dexamethasone + 500 mg of cyclophosphamide in 500 ml of 5% dextrose over 1-2 hours on day 1. Followed by daily administration of 100 mg of dexamethasone for the next 2 days . These pulses are repeated every 4 weeks. Major advantages seen with this therapy are quick healing of lesions, absence of side effects of corticosteroids.

69. TNF Alpha Inhibitors TNF alpha inhibitors from recent studies are showing possible mortality benefit , with one such study form Italy showing improvement in 10/10. Patients treated with a single dose of etanercept (50 mg) without significant side effects .

70. Other Lines: Tetracycline (2gr/day). Nicotinamide ( 1.5gr/day). Dapsone (100-300 mg /day). Rituximab (375 mg/m2 IV once weekly for 4 consecutive weeks). Plasmapheresis .

71. Conclusion Sudden severe alterations in the anatomy and physiology of skin consequent to generalized dermatoses can lead to disabling complications eventuating in the potentially fatal syndrome of acute skin failure. Understanding the etiopathogenesis of various systemic complications of acute skin failure and their prompt management in ICU on lines similar to that of burns can salvage many lives.