Difference between steven johnson syndrome , toxic epidermal

Difference between steven johnson syndrome , toxic epidermal

1. Difference between Steven Johnson Syndrome , Toxic Epidermal Necrolysis , Toxic Shock Syndrome and Staphylococcus Scalded Skin Syndrome

2. Steven Johnson Syndrome ( SJS ) & Toxic Epidermal Necrolysis ( TEN) Definition : severe mucocutaneous reactions characterized by extensive necrosis and detachment of epidermis . In US , the estimated incidences of SJS, SJS/TEN and TEN among children between 2009 – 2012 were 5.3 , 0.8 and 0.4 cases per million children. Ration male to female is 1: 2

3. SJS and TEN are differed based on total body surface area affected. SJS involves < 10 % of total body surface area TEN involves if > 30% of total body surface area SJS/TEN overlap involves between 10 – 30 % total body surface area

4. Wallace Rules of 9

5. Etiologies Drugs – limited up to 8 weeks of exposure Infection e.g mycoplasma pneumonia , CMV , URTI , Herpes Others Vaccinations Herbs Foods Radiotherapy Chemical exposure

6. Drugs Anticonvulsant ( carbamazepine , phenytoin , phenobarbitone , phenytoin, lamotrigine ) Antibiotics – cephalosporin , quinolones , aminopenicillin , trimethoprim /sulfamethoxazole NSAIDs Analgesic – Paracetamol Allopurinol Anti malarial Tranxenamic acid Anti cancer drugs – busulfan Corticosteroids Retinoids

7. Risk Factors HIV Malignancy Genetic factors – HLA ( human leukocytes antigen ) High doses and rapid introduction of medications SLE

8. Pathogenesis There are probably two major pathways involved: Fas-Fas ligand pathway of apoptosis has been considered a pivotal step in the pathogenesis of TEN. The Fas ligand ( FasL ), a form of  tumour  necrosis factor, is secreted by blood lymphocytes and can bind to the Fas ‘death’ receptor expressed by keratinocytes. Granule-mediated exocytosis via perforin and granzyme B resulting in cytotoxicity (cell death). Perforin and granzyme B can be detected in early blister fluid and it has been suggested that levels may be associated with disease severity.

9. Clinical Presentation Early signs/symptoms: Fever > 39 C Sore throat, difficulty swallowing Runny nose and cough Sore red eyes, conjunctivitis General aches and pains.

10. Later signs/symptoms: • Marked erythema of skin leading to papules, vesicles and necrosis started on the face neck and anterior trunk and may extend over the entire surface of the skin. May presented as b listers/macules/ flat atypical lesions , diffuse erythema • Mucosal involvement, including ocular, GI, GU, genital and upper and the epithelial cells of the lower respiratory tree.

11. Nicolsky’s sign : epidermal layer easily sloughs off when pressure applied to affected area

12. Eyes (conjunctivitis, less often corneal ulceration, anterior  uveitis)  — red, sore, sticky, photosensitive eyes Lips/mouth ( cheilitis , stomatitis) — red crusted lips, painful  mouth ulcers Pharynx , oesophagus  — causing difficulty eating Genital area and urinary tract — erosions, ulcers, urethritis , urinary retention Upper respiratory tract (trachea and bronchi) — cough and respiratory distress Gastrointestinal tract — diarrhoea .

13. Patient Evaluation and Diagnosis There are no universally accepted diagnostic criteria for SJS/TEN Diagnosis would be appropriate with the history and clinical findings.

14. Differential Diagnosis Staphylococcal scalded skin syndrome and toxic shock syndrome Erythema  multiforme , particularly erythema  multiforme major (with mucosal involvement) Mycoplasma infections Bullous systemic lupus erythematosus

15. Investigations : 1. skin biopsy Result shows keratinocyte apoptosis with detachment of the epidermal layer of the skin from the dermal layer 2. Blood CnS – negative 3. FBC 4. RP 5. LFT 6. Blood gases

16. Course of Illness The acute phase of SJS/TEN lasts 8–12 days. Repithelialisation of denuded areas takes several weeks, and is accompanied by peeling of the less severely affected skin

17. Treatment algorithm

18. Occupational and Physiotherapy

19. Complications Dehydration and acute malnutrition Infection of skin, mucous membranes, lungs (pneumonia),  septicaemia  (blood poisoning) Acute respiratory distress syndrome Gastrointestinal ulceration, perforation and intussusception Shock and multiple organ failure including kidney failure Thromboembolism and disseminated intravascular coagulopathy.

20. Long-term sequelae include: Pigment  change — patchwork of increased and decreased pigmentation Skin scarring, especially at sites of pressure or infection Loss of nails with permanent scarring ( pterygium ) and failure to regrow Scarred genitalia — phimosis (constricted foreskin which cannot retract) and vaginal adhesions (occluded vagina) Joint contractures Lung disease — bronchiolitis, bronchiectasis, obstructive disorders.

21. Prognosis SCORTEN is an illness severity score that has been developed to predict mortality in SJS and TEN cases. One point is scored for each of seven criteria present at the time of admission. The SCORTEN criteria are: Age > 40 years Presence of a malignancy (cancer) Heart rate > 120 Initial percentage of epidermal detachment > 10% Serum urea level > 10 mmol /L Serum glucose level > 14 mmol /L Serum bicarbonate level < 20 mmol /L.

22. The risk of dying from SJS/TEN depends on the score. SCORTEN 0-1 > 3.2% SCORTEN 2 > 12.1% SCORTEN 3 > 35.3% SCORTEN 4 > 58.3% SCORTEN 5 or more > 90%

23. Prognosis is best when:  Patients are <50 years of age  The total body surface area (TBSA) involved is low  Patients are transferred to a burn centre  Patients do not have sepsis  Patients do not require antibiotics.

24. Toxic Shock Syndrome

25. Definition : Streptococcal TSS is defined as an invasive infection secondary to group A streptococcus ( Streptococcus pyogenes ) associated with shock and multi-organ system failure occurring early in the course of the disease Organisms commonly responsible include group A streptococcus (  Streptococcus pyogenes  ),  or methicillin-sensitive (MSSA) or methicillin-resistant (MRSA)  Staphylococcus aureus  .

26. Can be divided to : Menstrual cause Non menstrual

27. Pathophysiology Toxic shock syndrome starts from a  localised  staphylococcal infection which produces the causative exotoxins . When tampons are used, bacteria can gain entery into the uterus via the cervix. They can also cause cuts in the vagina and permit access of bacteria into the tissues . It  may occur as a complication of other  localised  or systemic infections such as pneumonia, osteomyelitis, sinusitis, and skin wounds (surgical, traumatic or burns ). Streptococcal TSS is mediated by streptococcal pyrogenic exotoxins ( superantigens ) and virulence factors (M strains with M proteins 1 and 3) that activate the immune system to release inflammatory cytokines . The cytokines (TNF-alpha, interleukin [IL]-1, and IL-6) result in shock and multi-organ failure

28. Clinical presentation CDC case definition for toxic shock  syndrome requires presence of the following 5 clinical criteria : Temperature = > 38.9 c Low blood pressure (including fainting or dizziness on standing) : systolic BP ≤90 mmHg for adults or less than fifth percentile by age for children aged less than 16 yea Widespread red flat rash Shedding of skin, especially on palms and soles, 1–2 weeks after onset of illness Abnormalities in 3 or more of the following organ systems: Gastrointestinal: vomiting or diarrhoea Muscular: severe muscle pain Hepatic: decreased liver function Renal : raised urea or creatinine levels Hematologic: bruising due to low blood  plateletcount

29. Toxic shock syndrome diagnosis is confirmed if all 5 CDC clinical criteria are fulfilled. A probable case fulfils 4 of the 5 criteria.

30. Microscopy and culture on normally sterile sites (blood, CSF, pleural or peritoneal fluid, tissue, or throat) may be positive for group A streptococcus or Staphylococcus aureus . However, of patients with streptococcal TSS, 60% have positive blood cultures, and of patients with staphylococcal TSS,

31. Investigations FBC and differential show leukocytosis, anaemia , and thrombocytopenia • Renal function: elevated urea, creatinine, and haemoglobinuria are signs of renal failure. • Liver function: elevation of bilirubin or transaminases more than twice the normal upper limit • Albumin and calcium: commonly low on admission with streptococcal disease and throughout the clinical course • Lactic acid: elevated in severe sepsis and septic shock • Elevated creatine kinase (CK) suggests necrotising fasciitis or myositis. CK may also be elevated in staphylococcal TSS • Coagulation profile: shows increased prothrombin and partial thromboplastin times in staphylococcal disease in conjunction with DIC

32. Management The treatment starts with: Removing the source of infection  ie tampons, vaginal sponges, or nasal packing Draining and cleaning the site of wound. Start antibiotic

33. Supportive care- Intravenous fluids to treat shock and prevent organ damage Vasopressor for patients with very low blood pressure Dialysis in patients who develop renal failure Administration of blood products Oxygen and mechanical ventilation to assist with breathing

34. In suspected case Start Empirical Antibiotic Therapy IV clindamycin : 25 - 40 mg/kg per day in 3 divided dose + IV vancomycin : 40 mg/kg/ day in 4 divided doses

35. Confirmed case 1. Methicilin susceptible S. Aureus ( MSSA ) : IV clindamycin: 25 - 40 mg/kg per day in 3 divided dose + Oxacillin / nafcillin ( 100 -1 50 mg/kg per day in four divided doses ) 2. MRSA : IV clindamycin: 25 - 40 mg/kg per day in 3 divided dose + IV vancomycin: 40 mg/kg/ day in 4 divided doses Duration 1 -2 weeks

36. Prognosis Early diagnosis and appropriate treatment prevents progression of the disease and possible complications such as heart problems, acute renal failure, adult respiratory distress syndrome and disseminated intravascular coagulation . The mortality rate of toxic shock syndrome is approximately 5–15%, and recurrences have been reported in as many as 30–40% of cases

37. Staphylococcal scalded skin syndrome ( SSSS)

38.   An illness characterised by red blistering skin that looks like a burn or scald. It is caused by the release of two exotoxins ( epidermolytic toxins A and B) from toxigenic strains of the bacteria Staphylococcus aureus . A.k.a Ritter disease or Lyell disease when it appears in newborns or young infants.

39. Risk factors Children less than 5 years old Immunocompromised patients Pt with renal failure

40. Clinical Presentation It usually starts with fever, irritability and widespread  redness of the skin. Within 24-48 hours fluid-filled blisters form. These rupture easily, leaving an area that looks like a burn.

41. Rash characters : Tissue paper-like wrinkling of the skin is followed by the appearance of large fluid-filled blisters (bullae) in the armpits, groin and body orifices such as the nose and ears. Rash spreads to other parts of the body including the arms, legs and trunk. In newborns, lesions are often found in the diaper area or around the umbilical cord. Top layer of skin begins peeling off in sheets, leaving exposed a moist, red and tender area.  Nikolsky  sign is positive ( ie gentle strokes result in exfoliation)

42. Diagnosi s History and physical examination Skin biopsy- which shows  intraepidermal  cleavage at the granular layer CnS :  from skin, blood, urine or umblical cord sample (in a newborn baby)

43. DDx

44. Treatment A penicillinase -resistant, anti-staphylococcal antibiotic such as  flucloxacillin  is used . Other antibiotics include nafcillin , oxacillin , cephalosporin and clindamycin. Vancomycin is used in infections suspected with methicillin resistance (MRSA). Depending on response to treatment, oral antibiotics can be substituted within several days. The patient may be discharged from hospital to continue treatment at home. Corticosteroids slow down healing and hence are not given to patients with SSSS.

45. Other supportive treatments for SSSS include: Paracetamol when necessary for fever and pain. Monitoring and maintaining fluid and electrolyte intake. Skin care (the skin is often very fragile). Petroleum jelly should be applied to keep the skin moisturised . Newborn babies affected by SSSS are usually kept in incubators.

46. Referrence BMJ Best Practice.com Uptodate.com https://www.dermnetnz.org