PURPOSE OF REVIEW:

To review the newer, effective ophthalmologic treatments for acute Stevens-Johnson syndrome (SJS) as well as the emerging treatment options for patients with chronic, severe ocular surface damage from the disease.

RECENT FINDINGS:

Amniotic membrane transplantation (AMT) applied to the eyes and eyelids in the acute phase of SJS can prevent the devastating scarring and visual problems that characterize the chronic phase of the disease. The severity of ocular inflammation in the acute phase does not always correlate to the severity of skin and systemic involvement. Thus, it is crucial that all patients with SJS be evaluated by an ophthalmologist familiar with the current management of the disease, the potential urgency of the situation and the option of AMT. Although challenging, the severe, chronic ocular problems of SJS can be at least partially alleviated with autologous serum drops, mucous membrane grafting to replace scarred tarsal conjunctiva, specialized contact lenses (PROSE), conjunctival replacement surgery (COMET), limbal stem cell transplantation and kerotoprostheses.

SUMMARY:

Early AMT is an effective treatment of acute SJS. Emerging treatments offer increased hope for those who have already suffered damage from SJS, but emphasis on the prevention of damage in the acute phase is most crucial.

The objective of the current study was to characterize the epidemiology and resource use of U.S. children hospitalized with ophthalmologic disease secondary to erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). We studied children ages 5 to 19 years hospitalized in 2005 in 11 states, encompassing 38% of the U.S. pediatric population. Using International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified admissions of children with EM, SJS, or TEN and the presence of concurrent ophthalmologic disease, analyzed patient and hospitalization characteristics, and generated age- and sex-adjusted national estimates. We identified 460 children admitted with EM, SJS, or TEN, corresponding to 1,229 U.S. hospitalizations in 2005. Of the children with EM, SJS, or TEN, 60 (13.0%) had ophthalmologic disease, primarily (90.0%) disorders of the conjunctiva. Children with the highest proportions of ophthalmologic disease included those with mycoplasma pneumonia (26.7%), herpes simplex virus (15.6%), upper respiratory infection (13.9%), and lower respiratory infection (13.7%). Individuals with EM, SJS, or TEN and ophthalmologic disease were more likely than those without ophthalmologic disease to receive intensive care unit care (28.3% vs 17.0%, p = 0.03) and to be admitted to a children's hospital (63.3% vs 48.8%, p = 0.03). Ophthalmologic disease was also associated with a significantly longer median length of stay (6.0 days, interquartile range [IQR] 3-9 days vs 3.0 days, IQR 2-6 days, p < 0.001) and median hospital cost ($7,868, IQR $3,539-$17,440 vs $2,969, IQR $1,603-$8,656, p < 0.001). In children with EM, SJS, or TEN, ophthalmologic disease was most common in those with concurrent Mycoplasma pneumoniae and herpes simplex virus infections. Ophthalmologic disease was associated with considerably higher inpatient resource use in this population. Children with EM, SJS, or TEN should be screened and treated early for ophthalmologic disease to prevent morbidity and minimize long-term sequellae.

BACKGROUND:

Intravenous immune globulin (IVIG) is generally thought to be of relatively low risk for adverse events and some experts consider this to be the best treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis.

OBJECTIVE:

We evaluated the underlying cause of anemia and renal failure in 2 consecutive patients being treated with IVIG for Stevens-Johnson syndrome/toxic epidermal necrolysis.

METHODS:

This is a retrospective chart review.

RESULTS:

We present 2 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and severe hemolysis requiring blood transfusion who subsequently developed pigment nephropathy necessitating hemodialysis after treatment with IVIG. Both patients had antibodies to their ABO blood type detected in the eluate from their red blood cell membrane.

LIMITATIONS:

This is a retrospective review with only 2 cases.

CONCLUSIONS:

We propose that IVIG-associated hemolysis is an adverse reaction that may not be as rare as once thought, presenting as a mild decrease in hemoglobin and hematocrit. Antibodies to blood type A and B are given as part of pooled immune globulin and are considered to be the cause of hemolysis. More severe anemia requiring transfusion is less common, and the breakdown products produced by hemolysis can lead to pigment nephropathy and renal failure. We present methods by which this severe complication can be anticipated and managed more effectively.

Although most delayed drug hypersensitivity reactions are mild and show rapid improvement after drug discontinuation, there are severe systemic and/or cutaneous drug reactions which may be life-threatening. These entities are discussed here, namely DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Early detection of warning signs and symptoms may help to take appropriate measures precociously.

The purpose of this paper is to report a rare occurrence of Stevens-Johnson/Toxic epidermal necrolysis (SJS/TEN) overlap syndrome after the use of aceclofenac. A 38 year old healthy adult male presented with rapidly evolving rash over face and upper body with ulceration of buccal mucosa and breathlessness after taking aceclofenac tablet. Naranjo score for this adverse drug event was six, thereby making it a probable adverse drug reaction. Despite aggressive fluid resuscitation and use of antihistamines and systemic steroids, patient's health rapidly worsened and died within six hours of presentation. Aceclofenac induced SJS/TEN overlap is an extremely rare clinical association previously reported only once in medical literature. To the best of our knowledge, this is the first case report of such an association in the Indian population. We are presenting this case to highlight the serious adverse reactions possible from a routinely prescribed drug.

A 46 years old HIV reactive patient developed Stevens Johnson syndrome (SJS) probably due to nevirapine and/or co-trimoxazole. Patient was on zidovudine + lamivudine + nevirapine along with Co-trimoxazole since last two months. After 15 days, zidovudine was replaced with stavudine due to development of anemia. All these drugs were stopped after development of reaction. Temporal association was found between stavudine, lamivudine, nevirapine, cotrimoxazole and development of the reaction. Nevirapine and Co-trimoxazole were suspected to cause this reaction most probably due to associated hepatotoxicity and their common potential to cause SJS. In our case, patient died despite stopping of all medications.

Background Carbamazepine (CBZ) is broadly used for the treatment of epilepsy, neuropathic pain and other neurological diseases, owing to its effectiveness and low price. CBZ can induce Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). There are several studies that found an association between HLA-B*1502 and CBZ-induced SJS/TEN, especially in people of Thai origin. In Thailand the prevalence of HLA-B*1502 was found to be in the range 8.1-14 %. Objective This study aimed to determine if screening for HLA-B*1502 in Thai patients who were to receive CBZ is cost effective. Setting Srinagarind Hospital, Khon Kaen University, Thailand. Method A comparison between treatment cost of CBZ induced SJS/TEN and the HLAB*1502 screening costs in the Thai population. Main outcome measure Comparison of the costs of treatment of CBZ induced SJS/TEN and costs of HLA-B*1502 screening test. Results When persons having the HLA-B*1502 allele receive CBZ, the chance of developing SJS/TEN is as high as 88.1 %, while persons without the HLA-B*1502 allele do not develop SJS/TEN. Therefore, a model was calculated to compare the cost of treatment between HLA-B*1502 testing before giving CBZ and if the patients were not tested for HLAB*1502. It was found that screening 100 patients before giving CBZ would save an amount of 98,549.94 baht per 100 cases of CBZ-prescribed patients. Conclusion The screening for HLA-B*1502 allele before giving carbamazepine is cost effective. The results of the present study may also apply to other populations if the HLA-B*1502 frequency is high enough.

Imatinib mesylate is a tyrosine kinase inhibitor that targets the BCR-ABL, c-kit, and PDGF (platelet-derived growth factor) receptors. Imatinib is mainly indicated for chronic myeloid leukemia and gastrointestinal stromal tumors but is also prescribed by dermatologists for dermatofibrosarcoma protuberans, systemic sclerosis, and systemic mastocytosis, among other conditions. Most adverse effects are mild or moderate and therapy is generally well tolerated. Adverse skin effects are very common and include nonspecific manifestations such as edema and maculopapular rashes or eruptions of diverse types (lichenoid or psoriasiform lesions, acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and more). Identifying and properly treating these reactions can help optimize adherence to treatment and improve the prognosis of the underlying disease.

Rare but severe adverse drug reactions (ADRs) are an important issue in drug development and in the proper usage of drugs during the post-approval phase. The ability to predict patient susceptibility to severe ADRs would prevent drug administration to high-risk patients. This would save lives and ensure the quality of life for these patients, but occurrence of idiosyncratic severe ADRs had been very difficult to predict for a long time. However, in this decade, genetic markers have been found for several ADRs, especially for severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). In this review, we summarize recent progress in identifying genetic markers for SCARS and DILI, and discuss issues that remain unresolved. As for SCARs, associations of HLA-B*15:02 or HLA-A*31:01 and HLA-B*58:01 have been revealed for carbamazepine- and allopurinol-related Stevens-Johnson syndrome and toxic epidermal neclolysis, respectively. HLA-B*57:01 is strongly associated with abacavir-induced hypersensitivity syndrome. Several HLA alleles also demonstrate drug-specific associations with DILI, such as HLA-A*33:03 for ticlopidine, HLA-B*57:01 for flucloxacillin and HLA-DQA1*02:01 for lapatinib. Efforts should be continued to find other genetic markers to achieve high predictability for ADRs, with the goal being development of genetic tests for use in clinical settings.Journal of Human Genetics advance online publication, 2 May 2013; doi:10.1038/jhg.2013.37.