SJS-TEN: A possible cross allergy

between amoxycillin, ceftriazone and meropenem

presented by

Henry Foong FRCP

Ipoh, Malaysia

December 2, 2007

Consultant Dermatologist, Ipoh Specialist Hospital, Ipoh, Malaysia

Abstract A 20-year-old student was admitted to the ward for a dermatologic emergency with high fever and widespread erythematous macules, full-thickness epidermal detachment, mouth ulcers and genital erosions of 10 days duration. A clinical diagnosis of Stevens Johnson syndrome/ toxic epidermal necrolysis overlap was made. The possibility of cross reactivity and possible therapeutic interventions are discussed.
20-year-old man
10 days

A 20-year-old student was admitted to the ward for a dermatologic emergency with high fever and widespread erythematous macules, full-thickness epidermal detachment, mouth ulcers and genital erosions of 10 days duration. He had seen a general practitioner earlier for an upper repiratory tract infection and was put on amoxycillin. He subsequently developed high fever, mouth ulcers and rapidly developing rash on the face and trunk. The admitting physician stopped the antibiotic (amoxycillin) and put him on IV fluids, IV ceftriazone and IV hydrocortisone but his condition did not improve. More confluent flaccid blisters continue to develop and he was later transferred to another hospital 3 days later and was put on IV meropenem. This did not help either - epidermal detachment continue to deteriorate especially on the palms and soles. It was only after IV meropenem was withheld and replaced with oral erythromycin he subsequently improved with tailing doses of oral prednisolone.

Physical Examination

His general condition on admission was ill. He was febrile and dehydrated.

Extensive poorly defined erythematous macules with dark purpuric centers on the face, trunk and extremities. The distribution was almost symmetrical over the face and upper trunk. Marked erosions and crusts were also noted on the lips. Tongue ulcerations were severe on its border.

Few flaccid blisters were noted on the back of the trunk with large confluent areas of full detachment over lower trunk and gluteal areas. Similar extensive flaccid blisters were noted on the hands and feet. Nikolsky sign was positive, demonstrated by applying lateral pressure to blisters. There were severe erosions on the scrotum and penis as well. Fortunately, his conjunctiva and eyes were not affected.


Laboratory Data

Hb 14.7 gm% TWBC 4,600 (N76%, L19% E0%, M4% B1%) Platelet 167, 000

BU 14.5mmol/l

LFT normal

Swab was also sent for culture.


Skin biopsy shows almost entirely necrotic stratified squamous epithelium consistent with erythema multiforme. The superficial dermis contain mild to moderate perivascular mononuclear inflammatory infiltrate. No fibrinoid change was seen in the vessel wall.

Interpretation: erythema multiforme predominantly epidermal type


Stevens Johnson Syndrome/Toxic Epidermal Necrolysis Overlap

Reasons Presented

SJS and TEN are variants of the same process and is not an uncommon dermatologic emergency and often managed by junior doctors on admission. This is essentially drug-induced though GVHD and infection from mycoplasma pneumoniae are other recognised causes.

It is almost always a dilemma for the admitting physician to determine the culprit drug and to replace it other alternatives - history is vital here and patients may have seen few doctors before seeing the dermatologist/physician. Early diagnosis and determination of the offending drug is crucial. Cross reaction with other antibiotics is also possibility. The next dilemma is whether to use corticosteroids or IV Immunoglobulin G. Most studies have shown use of corticosteroids does not improve morbidity or mortality. In fact it may do more harm then good. In this patient however, we used short term high dose oral corticosteroids but in a tailing dose in view of cost constraints.

  1. Would you have used IV ceftriazone or IV meropenem as alternative antibiotics in an ill patient when a patient is allergic to amoxycillin? If not, what would be your choice?
  2. Do dermatologists still use corticosteroids to treat SJS/TEN?
  3. Would you have used IV immunoglobulins to treat this patient?
  1. Pierre-Dominique Ghislain M.D., Jean-Claude Roujeau, M.D. Treatment of severe drug reactions: Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis and Hypersensitivity syndrome. Dermatology Online Journal 8(1): 5 ( See abstract)
  2. Riichiro Abe, Tadamichi Shimizu, Akihiko Shibaki, Hideki Nakamura, Hirokazu Watanabe, and Hiroshi Shimizu Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome Are Induced by Soluble Fas Ligand Am J Pathol. 2003 May; 162(5): 1515–1520. ( see abstract)
  3. Robert S. Stern. Improving the Outcome of Patients With Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome. Arch Dermatol. 2000;136(3):410-411.
  4. Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC.Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000 Mar;136(3):323-7.
Keywords Stevens Johnson syndrome, toxic epidermal necrolysis, drug reaction, amoxycillin
Comments from Faculty and Members

David Elpern M.D., Williamstown, Massachusetts, USA on Dec 2, 2007

This is a brilliant case. Great teaching/learning value.

1) Why all the antibiotics in the absence of any + culture? I guess it is the way we practice these days. "Cover the patient." When the fever is likely a manifestation of the process that is causing the desquamation. There's a saying "Don't just do something -- sit there."

2) SJS/TEN may well just be a continuum. Same disease -- are you a lumper or a splitter?

3) I am not sure that this was cross-reactivity of the antibiotics. but could just have been the evolution of the disease. Most SJS/TEN will run a course -- by the time they got to the oral erythromycin he may have been getting better and the first drug was the one that caused the problem. Not enough evidence to implicate cross-reacitivty.

4) Systemic steroids -- no good evidence of value. IvIg -- yes, probably but what about the cost? If the patient looks like he is going to get better -- is the benefit/cost ratio worth it -- a very hard call. In the US -- yeah for a well-insured patient -- What about for an uninsured patient with an extra $30,000 or so in charges when he might well have gotten better anyway -- Really difficult calls -- and that's where experts come in - specialists who have managed more than two cases -- Yes, I remember a few over the past 25 years -- they all survived --

5) Maybe it's like MRSA -- in a certain subset of patients (sick to begin with) MRSA can be deadly -- in the general public, risk of death from MRSA is 1/50,000,000

Khalifa Sharquie MD, Professor of Dermatology, College of Medicine, University of Baghdad, Baghdad, Iraq on December 3, 2007

I think in this case the upper respiratory infection rather than multiple drugs allergies or drug cross sensitivity is the cause of the present problem. The management is mainly supportive after eliminating the cause like infection. There are no controlled studies showing that steroids are useful or harmful in treating TEN or SJS but sometimes we are obliged to give steroid just in case is useful. In my own experience I think systemic steroids can stop the progression of Erythema multiforme or at least reduce the duration of illness. Still there is a big dilemma.

Khaled el-hoshy MD, Troy, Michigan, USA on December 3, 2007

I would not use antibiotics, but closely monitor. I personally still use steroids @ 1mg/kg; IVIG works well but I have no personal experience. Burns unit care is needed with emphasis on IV fluids, & monitoring of hydration status.

Michael Bigby, MD, Associate Professor of Dermatology, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, MA, USA on December 4, 2007

  1. His course may have been natural history of SJS and not cross reactivity.
  2. I would not have given additional antibiotics.
  3. The weight of evidence is that corticosteroids may or may not be of value and IVIg is NOT!

Khalid Al Hawsawi M.D., Consultant Dermatologist, King Abdul Aziz Hospital, Makkah, Saudi Arabia on December 6, 2007

  1. Cross reaction do exist,so care should be taken.
  2. Use of systemic steroid depends on duration of illness. I prefer to use short course of systemic steroid immediately after stopping the offending agent but if the offending agent was stopped since several days, I do not recommend use of systemic steroid
  3. I.V immunoglobulins show excellent result.

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