|Year : 2013 | Volume
| Issue : 1 | Page : 3-9
Dermatologic manifestations in critically ill patients: Challenging task for an intensivist
Sukhminder Jit Singh Bajwa1, Kanwal Preet Singh1, Navdeep Kaur2
1 Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Banur, Punjab, India
2 Department of Dermatology, Columbia Hospital, Patiala, Punjab, India
|Date of Web Publication||17-Aug-2013|
Sukhminder Jit Singh Bajwa
Department of Anaesthesiologyand Intensive Care, Gian Sagar Medical College and Hospital, Ram Nagar, Banur, House No. 27A, Ratan Nagar, Tripuri, Patiala, Punjab
Source of Support: None, Conflict of Interest: None
Skin disorders are commonly encountered in intensive care unit and pose numerous diagnostic and therapeutic dilemmas to the attending intensivist. Variable presentation of a single critical illness or a common presentation of multiple critical illnesses is few of the challenging aspects of such dermatologic disorders. Lack of in-depth understanding of the dermatological manifestations of systemic diseases in critically ill patients is one of the prime factors for difficulty in accurate diagnosis and management. Services of a dermatologist are immensely helpful and essential in diagnostic and therapeutic management of such disorders. The present article reviews in detail the clinical profile, diagnostic measures and therapeutic interventions of various dermatologic disorders encountered in the critically ill patients.
Keywords: Critically ill, Drug reactions, Erythema multiforme, Erythroderma, Pemphigus vulgaris, Purpura
|How to cite this article:|
Bajwa SJ, Singh KP, Kaur N. Dermatologic manifestations in critically ill patients: Challenging task for an intensivist. J Med Soc 2013;27:3-9
|How to cite this URL:|
Bajwa SJ, Singh KP, Kaur N. Dermatologic manifestations in critically ill patients: Challenging task for an intensivist. J Med Soc [serial online] 2013 [cited 2020 Oct 21];27:3-9. Available from: https://www.jmedsoc.org/text.asp?2013/27/1/3/116620
| Introduction|| |
Intensivists are faced with numerous challenges during the management of critically ill patients. Though, there are numerous diseases which becomes difficult to diagnose in patients during their stay in intensive care unit (ICU), the dilemmas presented by the cutaneous and dermatological disorders is sometimes difficult to overcome. Lack of deep understanding of the dermatological manifestations of systemic diseases in critically ill patients is one of the prime factors for difficulty in accurate diagnosis. It would be extremely difficult to treat dermatological disorders as these require the specialist services of a dermatologist. The skin plays a key role in maintaining homeostasis, thermoregulation containment of body fluids and protection of internal organs from environmental insults. The skin is readily available for clinical and physical examination, so inspection often provides important clues to the underlying disease.  However, the same cannot be held true for critically sick patients due to interplay of multiple factors and the above mentioned challenges. As such, there is a strong need felt among intensivists for reviewing these clinical diagnostic entities for better management of patients in ICU that develop dermatological manifestations. The aim of the present article is to review these difficult diagnostic scenarios and their subsequent management and the present article will focus on following broad areas relevant to critically ill patients:
- Drug reactions
- Life threatening dermatoses
- Common skin disorders in ICU
| Drug Reactions|| |
An adverse drug reaction may be defined as an undesirable clinical manifestation resulting from administration of a particular drug; this includes reaction due to overdose, predictable side-effects and unanticipated adverse manifestations.  Adverse drug reactions may be also be considered as an inevitable price the physicians have to pay for the benefits of modern drug therapy.  Patients receiving multiple drug therapy, such as the critically ill, are more prone to develop a drug eruption [Table 1]. Patients with severe debilitating diseases, multi-organ dysfunction, and depressed immunity such as in acquired immune deficiency syndrome (AIDS) may appear to be at a greater risk of developing adverse drug reactions.  Generally, speaking these adverse drug reactions can be classified as follow: 
Pattern of Drug Eruptions
The practice of unavoidable polypharmacy in ICU invariably increases the potential possibilities of severe drug eruptions and associated lesions. Many a times, these lesions can be easily confused with manifestations of some systemic illness. These eruptive patterns have to be recognized for appropriate medication and management [Table 2].
|Table 2: Morphological patterns of drug eruptions and commonly incriminated drugs |
Click here to view
Clinically, erythema multiforme (EM), involves macular, papular or urticarial lesions as well as classical iris or target lesions described preferentially on the distal extremities.  EM can possibly be caused by viral infections (Herpes Simplex, Mycoplasma, AIDS, Adenovirus, Cytomegalo Virus, Mumps, Polio, Variola, Varicella), Bacterial infections, Fungal infections, Drugs, Carcinomas/lymphomas, Pregnancy, Sarcoidosis, or Lupus erythematosus.
Steven Johnson Syndrome
Steven Johnson syndrome (SJS) comprises of extensive EM of trunk and mucous membranes accompanied by fever, malaise, myalgia and arthralgia. 
Toxic Epidermal Necrolysis (TEN) (also known as Lyell Syndrome) first described in 1956 is characterized by extensive sheet like skin erosions with widespread purpuric macules or flat atypical target lesions accompanied by severe involvement of conjunctival, corneal, irideal, buccal, labial, and genital mucous membranes. ,
Numerous drugs have been incriminated in causation of EM which has been enumerated in [Table 3].
Lesions are dull red, flat or slightly raised maculo papules.  Typically target lesions are seen which have 3 zones: Central area of dusky erythema or purpura, middle paler zone of oedema and an outer ring of erythema with a well-defined edge. Lesions appear in successive crops and fade in 1-2 weeks. Classically, back of the hands, palms, wrist, feet, extensor aspect of the elbows, and knees are affected.
The clinical utility of systemic steroids is still debated.  For severe cases, prednisolone at an initial dosage of 30-60 mg/day decreasing over a period of 1-4 weeks is usually given. Long term prophylactic use of acyclovir is quite effective in recurrent EM due to herpes simplex. Thalidomide has been used in a few cases to prevent relapses of recurrent EM.  Other drugs which have been used with variable success include, dapsone, azathioprine and mycophenolate mofetil. 
There is a fair degree of overlap between SJS and TEN.  SJS may evolve into TEN and several drugs mentioned earlier can produce both entities. SJS, with occasional skin blisters and erosions covering less than 10% of the body surface area (BSA) is differentiated from TEN in which typically sheet like erosions involve more than 30% of the BSA. 
Clinical Features of SJS and TEN
Clinically these pathologies are characterized by:
Prodrome of fever, nausea, vomiting, diarrhea, malaise, headache, cough, sore throat, myalgia and arthralgia 1-14 days before the skin eruption. 
- Severe acute blistering disease associated with significant morbidity and mortality
- There is often a recent history of drug ingestion.
- SJS: It is characterized by wide-spread red/purpuric macules or target lesions with sub-epidermal detachment of less than 10% of BSA at worse, mucosal erosions frequent [Table 4].
- TEN: It presents as a variant of same process with epidermal detachment greater than 30% of the BSA [Table 4].
There is appreciable mortality as a result of TEN, increasing from 5% in SJS to 10-15% in transitional SJS-TEN and 30-40% in TEN. Acute respiratory distress syndrome and multiple organ failure are the usual causes of death.  They are often precipitated by sepsis with septicemia mainly resulting from Staphylococcs aureus and Pseudomonas aeroginosa.  Other causes of higher mortality are pulmonary embolism and gastrointestinal bleeding. Prognosis can be predicted to a large extent with the help of Scorten prognosis score [Table 5].
One point awarded for each parameter, Severity of illness score for toxic epidermal necrolysis (SCORTEN) derived by totaling scores.
Management should include but is not limited to 
Life Threatening Dermatoses in Dermatology
- Patient should be treated in intensive care or burns unit
- Beds should be air fluidized
- Maintenance of fluid and electrolyte balance (replace 5 L/day)
- Maintenance of body temperature
- Maintenance of nutrition and oral hygiene
- Frequent ophthalmological assessment should be carried out
- Frequent culture of erosions/blood cultures is mandatory
- Topical cleansing/antibacterial agents should be used.
- Paraffin gauzes
- Biological dressings.
Dermatology is usually thought of as an out-patient speciality with low mortality. However, some skin conditions can be very severe and the condition itself, or due to associated complications of the illness or treatment may cause the patient to require intensive care. Some of these clinical entities can be enumerated as under:
- Pemphigus vulgaris
- Exfoliative erythroderma
- Generalized pustular psoriasis (GPP)
- Necrotizing fasciitis
Pemphigus vulgaris is a rare life threatening autoimmune disease characterized by intraepithelial vesicles and bullae. Stratified squamous epithelium of both skin and mucosal surface is involved. The pathogenic process involves circulating Immunoglobulin G (IgG) antibodies directed against the intercellular substance of the epidermis.  It is a disease of middle age that affects children rarely, but patients are younger at presentation in India than in the western countries. 
It presents as oral lesions in 50-70% of patients which precede cutaneous lesions by a month.  Cutaneous lesions with predilection for scalp, face, axilla, groins, and pressure points develop. Flaccid blisters filled with clear fluid are often seen in this clinical entity. Nikolsky sign is positive in pemphigus vulgaris.
Disease activity generally decreases with time and most relapses occur in the first 2 years of diagnosis. 
Potent topical or intra-lesional steroids may reduce the requirement of oral steroids. Potassium permanganate wash and topical antiseptics may reduce the risk of cutaneous infection.
Prednisolone 1-1.5 mg/kg/day is helpful in controlling the disease.  Combination of azathioprine and prednisolone is more useful.  Monthly intravenous pulses of cyclophosphamide with dexamethasone combined with low dose oral cyclophosphamide have been used with great success.  Tetracycline, cyclosporine, mycophenolate mofetil, plasmapheresis, IgG have been helpful in some cases.
Erythroderma is the term applied to any inflammatory skin disease that affects more than 90% of the body surface. Generally it is caused by: 
- Hereditary disorders like ichthyosiform erythroderma, Pityriasis Rubra Pilaris (PRP)
- Other skin diseases like Lichen Planus (LP), crusted scabies, dermatophytosis
Most patients complain of pruritus. The entire skin is red, scaly, indurated. Excoriations, peripheral edema, moderate symmetric lymph node enlargement are common. Mucous membranes usually are spared. There may be symptoms of orthostatic hypotension owing to increased insensible water loss. Congestive heart failure due to marked circulatory shunting through the skin may develop in patients with pre-existing cardiac disease. Thermoregulatory dysfunction can result in relative hypothermia and chills.
Urea, electrolyte levels and fluid balance should be monitored. All non-essential drugs should be withdrawn. Soothing emollient cream or mild topical steroid is the first line of treatment.  Then treat the specific causes.
Eruption may be ushered in by a sensation of burning. The skin becomes dry/tender andis followed by high fever, malaise. Pre-existing psoriatic lesions become fiery and develop pinpoint pustules. Sheets of erythema and pustulation spread to involve previously unaffected skin, flexures and genitals. 
- Death can occur in the acute stage
- Hypoalbuminemia and hypocalcaemia may lead to Renal Tubular necrosis 
- Deep Venous Thrombosis (DVT) in leg may cause pulm embolism
- Staphylococcal infection may occur
- Inflammatory polyarthritis is common.
Management includes withdrawal of provocative factors, General measures to control symptoms, bed rest, bland local application, fluid, and protein replacement. Topical therapy can be used in the form of bland creams, but lotions are best. Weak corticosteroid creams may also be helpful. Systemic therapy can be administered in the form of retinoids which are considered as the treatment of choice. Response to high dose of acitretin (1 mg/kg/day) may be rapid and lower doses (0.5-0.75 mg/kg/day) may be sufficient to maintain control.  Psoralen and Ultra-Violet A therapy is effective in acute and sub-acute GPP.  Methotrexate is also effective. Oral or parenteral corticosteroid should be used only when urgent control of metabolic complications is needed. The short term effects of prednisolone are excellent. 
Necrotizing fasciitis may follow entry of Group A Streptococci, S. aureus, Aeromonas, Vibrio vulnificus including at least one anaerobic organism into skin most commonly on head and neck/limbs. 
Patients present with hot, tender area of swelling, which is erythematous occasionally dusky. Bullae and necrosis of underlying tissue may intervene. 
Treatment includes surgical debridement and intravenous antibiotics.
| Common Cutaneous Manifestations in ICU|| |
Candidiasis is an infection caused by the yeast Candida albicans. Superficial infections of the mucous membranes and skin are most important and more common in ICU setting. Serious involvement of internal organs may result in septicemia, endocarditis and meningitis.
The commonest pattern is oral thrush characterized by sharply defined patch of creamy, curd like pseudo-membrane, which when removed leaves an erythematous area. Buccal mucosa, gums, and palate are commonly affected but in immunocompromised patients tongue may also be involved.
Most cases of cutaneous candidiasis occur in the skin folds or where occlusion from clothing or dressings produces abnormally moist conditions. Satellite lesions are classical. In patients of AIDS, hematologic malignancies, indwelling intravenous catheter or malnutrition, systemic candidiasis may occur. 
Superficial candidiasis should be topical with azole antifungals and the area should be kept clean and dry.  Systemic candidosis should be treated with systemic agents like Amphotericin B, Fluconazole and Itraconazole.
Traumatic Lesions During Intensive Care
The complex technology now involved in intensive care includes a number of invasive procedures that can cause cutaneous lesions.  Continuous arterial catheterization may lead to bruising or even local or peripheral skin necrosis. Phlebitis may also occur.
Pressure sores occur as a result of a localized area of necrosis caused by ischemia, resulting from compression of soft-tissue between a bony prominence and an external surface. The elderly are especially susceptible.  The prevalence of pressure sores have decreased in the hospital settings by the introduction of various measures in 1990's. 
Contact dermatitis is caused by allergens or irritants. Tape, cleansing agents, topical medications may be the offender.
Clinical features-Circumscribed eruption confined to the area of contact is the prime feature. It can present with erythema, vesico-bullous eruption, which may be exuding.
Treatment includes removal of allergen and application of steroid cream.
It results due to obliteration of the eccrine sweat duct. They differ in clinical forms due to different levels at which disruption occurs.  It is commonly seen in bedridden patients with fever.
Miliaria crystalline: Seen as clear dewdrops. It is characterized by small, very superficial vesicles without surrounding inflammation.
Miliaria rubra: Seen as pruritic erythematous papules. Areas such as back of the patients lying on bed, antecubital and popliteal fossa are the sites of predilection.
Loose cotton clothing is advisable. Area should be kept dry. Oral antihistamines, medium potency topical steroid or topical antipruritic lotions are helpful. 
It presents as bluish or purple discoloration of the skin varying in size which is non-blanchable. It results from hemorrhage into the skin or mucous membranes. The causes of pupura can be classified as follow [Table 6]. 
Disseminated Intravascular Coagulation/Purpura Fulminans
This is the most deadly clinical manifestation which an intensivist encounters during the routine clinical ICU practice. It is clinically characterized by:
- Fever, hypotension, extensive skin necrosis associated with evidence of disseminated intravascular coagulation (DIC)
- Large irregular areas of purpura especially, over the extremities
- Skin lesions are tender, enlarge rapidly and may involve into hemorrhagic bullae with subsequent necrosis. Necrosis of the entire extremity may develop.
- Pulmonary, hepatic, renal failure, Gastro-intestinal (GI) bleeding and hemorrhagic adrenal infarction may occur. 
| Conclusion|| |
Dermatologic diseases are extremely difficult to diagnose with precision without adequate in-depth knowledge of various pathophysiological aspects and clinical presentation of the diseases. The relative shortage of dermatologists in our country mandates that every physician should be well aware of the management of common skin diseases. Intensivists have to gear up to diagnose, prevent and manage various dermatological disorders in ICU as they can directly or indirectly impact the outcome in critically ill patients.
| References|| |
|1.||Shen HN, Lu CL. Skin and soft tissue infections in hospitalized and critically ill patients: A nationwide population-based study. BMC Infect Dis 2010;10:151. |
|2.||Edwards IR, Aronson JK. Adverse drug reactions: Definitions, diagnosis, and management. Lancet 2000;356:1255-9. |
|3.||Nolan L, O′Malley K. Adverse drug reactions in the elderly. Br J Hosp Med 1989;41:446, 448, 452-7. |
|4.||Pirmohamed M, Park BK. HIV and drug allergy. Curr Opin Allergy Clin Immunol 2001;1:311-6. |
|5.||Anderson JA. Allergic reactions to drugs and biological agents. JAMA 1992;268:2844-57. |
|6.||Drago F, Rampini E, Rebora A. Atypical exanthems: Morphology and laboratory investigations may lead to an aetiological diagnosis in about 70% of cases. Br J Dermatol 2002;147:255-60. |
|7.||Nicolis GD, Helwig EB. Exfoliative dermatitis. A clinicopathologic study of 135 cases. Arch Dermatol 1973;108:788-97. |
|8.||Shipley D, Ormerod AD. Drug-induced urticaria. Recognition and treatment. Am J Clin Dermatol 2001;2:151-8. |
|9.||Ferguson J, Frain-Bell W. Pigmentary disorders and systemic drug therapy. Clin Dermatol 1989;7:44-54. |
|10.||Webster GF. Pustular drug reactions. Clin Dermatol 1993;11:541-3. |
|11.||Cohen AD, Cagnano E, Halevy S. Acute generalized exanthematous pustulosis mimicking toxic epidermal necrolysis. Int J Dermatol 2001;40:458-61. |
|12.||Brenner S, Wolf R, Ruocco V. Drug-induced pemphigus. I. A survey. Clin Dermatol 1993;11:501-5. |
|13.||Sanchez NP, Van Hale HM, Su WP. Clinical and histopathologic spectrum of necrotizing vasculitis. Report of findings in 101 cases. Arch Dermatol 1985;121:220-4. |
|14.||Schofield JK, Tatnall FM, Leigh IM. Recurrent erythema multiforme: Clinical features and treatment in a large series of patients. Br J Dermatol 1993;128:542-5. |
|15.||Côté B, Wechsler J, Bastuji-Garin S, Assier H, Revuz J, Roujeau JC. Clinicopathologic correlation in erythema multiforme and Stevens-Johnson syndrome. Arch Dermatol 1995;131:1268-72. |
|16.||Wolkenstein P, Revuz J. Toxic epidermal necrolysis. Dermatol Clin 2000;18:485-95. |
|17.||Nethercott JR, Choi BC. Erythema multiforme (Stevens-Johnson syndrome) - Chart review of 123 hospitalized patients. Dermatologica 1985;171:383-96. |
|18.||Hay R, Bendeck SE, Chen S. Skin Diseases. In: Jamison DT, Breman JG, Measham AR, editors. Disease Control Priorities in Developing Countries. 2 nd edition. Washington (DC): World Bank; 2006. Chapter 37. Available from: http://www.ncbi.nlm.nih.gov/books/NBK11733/. [Last accessed on 2013 Feb 22]. |
|19.||Moisson YF, Janier M, Civatte J. Thalidomide for recurrent erythema multiforme. Br J Dermatol 1992;126:92-3. |
|20.||Pavloviæ MD, Karadagliæ DM, Kandolf LO, Mijuskoviæ ZP. Persistent erythema multiforme: A report of three cases. J Eur Acad Dermatol Venereol 2001;15:54-8. |
|21.||Schulz JT, Sheridan RL, Ryan CM, MacKool B, Tompkins RG. A 10-year experience with toxic epidermal necrolysis. J Burn Care Rehabil 2000;21:199-204. |
|22.||Roujeau JC, Chosidow O, Saiag P, Guillaume JC. Toxic epidermal necrolysis (Lyell syndrome). J Am Acad Dermatol 1990;23:1039-58. |
|23.||Roujeau-JC, Revuz J. Intensive care in dermatology. In: Champion RH, Pye RD, editors. Recent Advances in Dermatology. Vol. 8. Edinburgh: Churchill Livingstone; 1990. p. 85-99. |
|24.||Wilson C, Wojnarowska F, Mehra NK, Pasricha JS. Pemphigus in Oxford, UK, and New Delhi, India: A comparative study of disease characteristics and HLA antigens. Dermatology 1994;189 Suppl 1:108-10. |
|25.||Ryan JG. Pemphigus. A 20-year survey of experience with 70 cases. Arch Dermatol 1971;104:14-20. |
|26.||Kyriakis KP, Tosca AD. Epidemiologic observations on the natural course of pemphigus vulgaris. Int J Dermatol 1998;37:215-9. |
|27.||Carson PJ, Hameed A, Ahmed AR. Influence of treatment on the clinical course of pemphigus vulgaris. J Am Acad Dermatol 1996;34:645-52. |
|28.||Kanwar AJ, Kaur S, Thami GP. Long-term efficacy of dexamethasone-cyclophosphamide pulse therapy in pemphigus. Dermatology 2002;204:228-31. |
|29.||Akhyani M, Ghodsi ZS, Toosi S, Dabbaghian H. Erythroderma: A clinical study of 97 cases. BMC Dermatol 2005;5:5. |
|30.||Baker H. Pustular psoriasis. Dermatol Clin 1984;2:455-70. |
|31.||Warren DJ, Winney RJ, Beveridge GW. Oligaemia, renal failure, and jaundice associated with acute pustular psoriasis. Br Med J 1974;2:406-8. |
|32.||Lowe NJ, Lazarus V, Matt L. Systemic retinoid therapy for psoriasis. J Am Acad Dermatol 1988;19:186-91. |
|33.||Henseler T, Wolff K, Hönigsmann H, Christophers E. Oral 8-methoxypsoralen photochemotherapy of psoriasis. The European PUVA study: A cooperative study among 18 European centres. Lancet 1981;1:853-7. |
|34.||Ryan TJ, Baker H. Systemic corticosteroids and folic acid antagonists in the treatment of generalized pustular psoriasis. Evaluation and prognosis based on the study of 104 cases. Br J Dermatol 1969;81:134-45. |
|35.||Umbert IJ, Winkelmann RK, Oliver GF, Peters MS. Necrotizing fasciitis: A clinical, microbiologic, and histopathologic study of 14 patients. J Am Acad Dermatol 1989;20:774-81. |
|36.||Barker FG, Leppard BJ, Seal DV. Streptococcal necrotising fasciitis: Comparison between histological and clinical features. J Clin Pathol 1987;40:335-41. |
|37.||Sobel JD, Vazquez J. Candidiasis in the intensive care unit. Semin Respir Crit Care Med 2003;24:99-112. |
|38.||Bajwa SJ, Kulshrestha A. Fungal infections in intensive care unit: Challenges in diagnosis and management. Ann Med Health Sci Res 2013;3:238-44. |
|39.||Perneger TV, Héliot C, Raë AC, Borst F, Gaspoz JM. Hospital-acquired pressure ulcers: Risk factors and use of preventive devices. Arch Intern Med 1998;158:1940-5. |
|40.||Torrance C, Maylor M. Pressure sore survey: Part one. J Wound Care 1999;8:27-30. |
|41.||Hölzle E, Kligman AM. The pathogenesis of miliaria rubra. Role of the resident microflora. Br J Dermatol 1978;99:117-37. |
|42.||Haas N, Martens F, Henz BM. Miliaria crystallina in an intensive care setting. Clin Exp Dermatol 2004;29:32-4. |
|43.||Betrosian AP, Berlet T, Agarwal B. Purpura fulminans in sepsis. Am J Med Sci 2006;332:339-45. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]