DRESS; Drug reaction with eosinophilia and systemic symptom, is a severe adverse drug-induced reaction or drug induced hypersensitivity which is a potentially life- threatening drug hypersensitivity syndrome mostly associated with anticonvulsants dapsone, allopurinol,and long acting sulfonamides . Drugs such as ; sulfonamides, Phenobarbital,sulfasalazine, carbamazepine and phenyoin induce Dress Syndrome .Drug induced hypersensitivity syndrome presents clinically as an extensive mucocutaneous rash ,fever, lymph node enlargement, internal organ involvement ,hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes. The pathogenesis is related to specific drugs, especially aromatic anticonvulsants, altered immune response ,sequential reactivation of herpes virus and association with HLA alleles. Withdrawal of offending drug and use of corticosteroids are the most important steps in the treatment of this syndrome.The diagonosis of DRESS is challenging due to diversity of cutaneous eruption and organs involved .Regi SCAR scoring system is used that grades DRESS cases as no ,possible, probable or definite to classify cases reported in the literature. We conclude that such syndrome should be diagonised as soon as possible and steps should be taken to eradicate or overcome such life threatening syndrome its better for patient to treat illness when it is in its early rather than it becomes worst.
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KEYWORDS - Hypersensitivity , Adverse drug reaction ,Regi SCAR , anticonvulsants .
The Life threatening DRESS (drug rash with eosinophilia systemic symptoms ) syndrome is a severe adverse drug reaction accompanied by symptoms like fever, lymph node enlargement ,skin rash, internal organ involvement , hepatitis , atypical circulating lymphocytes, exanthema , and lymphadenopathy (1) . It was previously named as Drug Hypersensitivity Syndrome. It refers to the condition of hypersensitivity to certain medications and such condition is severe and result in adverse drug reaction characterised by skin rashes , fever and organ involvement (2) (3) (4) .
The DRESS Syndrome was first introduced by Bocquet (1996) (5). Fever, skin rash ,internal organ involvement and lymphadenopathy are the marked main manifestions to DRESS . The main organ involved is liver followed by kidney and lungs and drugs which results in causing this syndrome are anti convulsants , dapsone , sulphonamides , allopurinol , minocycline , anti tuberculosis drugs , phenobarbital and phenytoin . The pathophysiology of DRESS is still not clear as it is multifactorial disease involving immunological mechanisms and particular drug detoxification pathway . The infections like Human Herpes virus 6 (HHV-6) and immunological imbalance are causative factors which leads to high risk of this syndrome (6)
The overall mortality rate in DRESS syndrome is 10% and hence it occurs in patients with multi organ involvement . To overcome this mortality rate and problems suffered by the people an effort is made in developing Regi scoring system with the help of which one can determine the seversity of this syndrome as this system has been designed to grade DRESS cases as "no", "possible","probable" or "definite" (7).
In this article we will be covering the problems (causes , symptoms and factors responsible) for DRESS syndrome which people have been suffering from last few decades and steps we can take to overcome this problem( treatment and management) related aspects where as suggestions ,steps as propectives to overcome this severe life threatening syndrome.
1. DRESS Syndrome (Drug Reaction Eosinophilia and Systemic Symptoms) is life threatening syndrome which is associated with fever, skin rashes and eruptions
2. The main causative agents of DRESS are Human Herpes virus (HHV -6),immunological imbalance ,culprit drugs (allopurinol, anti tuberculosis drugs ,phenytoin and Phenobarbital ) and corticosteroids .
3. The main treatment for DRESS is withdrawal of culprit drugs ,avoidance to corticosteroid treatment and serology of the viruses responsible such as (HHV - 6) should be checked.(7)
Signs and Symptoms -
DRESS Syndrome (life threatening and severe adverse drug reaction ) is characterised by several symptoms such as skin rashes , internal organ enlargement , multiple organ enlargement ,fever, exanthema ,atypical circulating lymphocytes ,lymphadenopathy and hepatitis .Out of these fever, skin rash ,lymph node enlargement are the signs which start occurring within 8th weeks after initiation of the therapy .Haematological abnormalities ,especially eosinophilia and mononucleosis like atypical lymphocytosis are also commonly occurring symptoms during therapy (1).During the drug regimen treatment the first sign occurring is fever which occurs in the 8 week of the treatment due to prolong drug exposure the patient suffers from long lasting skin eruptions which further leads to dermatitis followed by nephritis myocarditis (8).
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There are many factors which are responsible for causing DRESS Syndrome like: Anticonvulsants including Phenobarbital which is third of the drugs causing DRESS (1), carbamazepine is the highest inducers of DRESS(7) and last not the least allopurinol which is the responsible for severe toxic reaction called allopurinol induced reaction (9),beyond these drugs there are many other drugs which also contribute to this syndrome such as calcium channel blockers ,anti inflammatory drugs ,anti retroviral drugs ,metronidazole ,terbinafine and captopril (8),hence they all are responsible for increasing morbidity and morality .
Some viruses such as (HHV-6) human herpes virus are responsible for DRESS syndrome. HHV-6 reactivation is known to be a potential contributor for DRESS development. Beyond this there are many other viruses which are responsible too such as Cytomegalovirus reactivation and Paramyxovirus infection. These all above mentioned are the factors which lead to symptoms showing DRESS , hence it is better to recover the syndrome in early stage as soon as possible otherwise it may lead to life threatening stage symptoms finally resulting in death .(7)
DIAGNOSIS- ( multi organ hypersensitivity syndrome)
As in DRESS Syndrome multi organs are involved hence it becomes difficult to diagnose. As it is a life threatening syndrome it becomes important to diagnose as soon as possible to overcome such syndrome , Hence effort is made to develop Scoring system that is known as Regi SCAR scoring system. This system constitutes European registry of severe cutaneous adverse reaction (SCAR) , it also includes Stevens -Johnson syndrome , epidermal necrosis and finally DRESS(14).With the help of this system we can easily grade DRESS cases as "no", "possible", "probable" or "definite" (7) .Through this Regi scoring system we will able to analyse the seversity of the syndrome and will be able to provide drug regimen as per required. As we know its difficult to diagnose DRESS as it is multi organ hypersensitivity syndrome there are several laboratory tests which will distinguish DRESS syndrome from the other occurring syndromes tests involved are liver function tests , complete blood cell count , urinalysis,and serum creatinine , skin biopsy and thyroid stimulating hormone level tests (8).
As DRESS (Drug Rash Eosinophilia and systemic symptoms ) syndrome is rather distinct severe adverse drug reaction characterised by fever , skin eruptions , dermatitis , nephritis organ involvement specially liver followed by kidney and lungs finally death if not treated. It is very important to manage this life threatening disease, various steps are taken to prevent this disease such as
1.Identification of culprit drugs and their withdrawal such as anticonvulsants including Phenobarbital which leads to DRESS , Carbamazepine (main potential contributor of DRESS)(7) and Allopurinol responsible for causing a severe toxic reaction called allopurinol induced DRESS syndrome(9) . Other inducers are calcium channel blockers , Terbinafine, Metronidazole , Antiretroviral drugs and Anti tuberculosis drugs(8)
2. To avoid reactivation of viruses such as (HHV-6)human herpes virus ,cytomegalovirus and paramyxovirus infection as they are the one resulting in DRESS syndrome. Hence serology of such viruses should be cheked.(7)
3.Avoid corticosteroid treatment , as it will help in reducing symptoms related to syndrome
4. Use of antipyretics help in overcoming fever and use of topical steroids will helping in overcoming skin related problems like skin rashes ,eruptions etc(8)
5. Avoid re exposure of such inducing drugs to patients and adequate treatment alternatives should be found when possible in case of emergency (8)
As we all know that DRESS syndrome is life threatening hence known as distinct adverse drug reaction as well as hypersensitivity reaction , it leads to many severe signs and symptoms if kept untreated it leads to death . The mortality rate due to DRESS is reported to be 10 % which can increase further if no steps are taken to eradicate it .There are many steps which can be taken for eradicating such syndrome and also help in reducing people sufferings . we know that the hospitals plays an important role in humans life, it is a place where patient receives proper care to overcome his /her sufferings, hospitals are known to be professional health care centres managed by physician/ nurses ,which results in re gaining of patients normal health on the other hand it may worsen patients condition if not treated in correct way.
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Some key points should be kept in mind in order to avoid worsening conditions
. Don't prescribe drugs to the patient without knowing his /her medical history.
Knowledge regarding the previous treatment if any.
Before deciding the prescription, stage of syndrome should be known (early, middle or last).
Safety profile of the drugs should be checked before prescribing to the patient .safety profile includes drug (effects or side effects) if any.
Age, sex of the patient should be kept in mind while prescribing .specially in case of pregnancy.(10)
On the other hand its the duty of physician and clinician to make decisions regarding timely adjustment of drug therapy, such decisions are helpful in conditions like : when the response of the patient towards the prescribed drug is slow or when the patient develops resistant property towards prescribed drug which may result leads to drug -drug interactions further it may worsen the conditions(11)
. Hence there are some ideal properties of drug, drugs with such properties only should be prescribed . Properties are as follows :
1. Drug should not show any kind of interactions or reactions when come in contact with body fluids etc
2. Significant pharmacokinetic variability
3. Effective cost
4 Easy availability
5 Established target concentration range
6 Reasonable relationships between plasma concentration and clinical effect (12)
It also become very important to educate the people regarding safety use of drugs and awaring them regarding the drawbacks which can occur due to misuse , overuse ,abuse of the drugs and intake of non prescribed drugs .Steps should be taken to spread awareness like : seminars should be conducted in village /city side , poster displaying , awareness debates / lectures ,awareness camps ,advertisements etc all this will help in eradicating such life threatening DRESS syndrome. Last but not the least one should also concentrate towards the detection ,assessment , understanding and prevention of adverse drug reactions which may be caused due to intake of non prescribed drugs , drug overdose ,misuse or abuse ,lack of knowledge, hence pharmacovigilance helps in overcoming such conditions and plays role in improving the safe and rationale use of medicines which results in good patient and public health(13) . Due to pharmacovigilance only un necessary sufferings by the patients are prevented ,it also decreases the financial loss sustained by the patients due to inappropriate and unsafe use of drugs .hence this system should also be followed throughout so that the syndromes like DRESS can be eradicated which will help in decreasing mortality rate and make the world healthier to survive .
In this above article we have done study regarding DRESS syndrome in expanded way, it covers (causes ,factors responsible ,issues and steps taken to diagnose ,manage to overcome this life threatening syndrome and further the prospectives which we can put forward to solve or eradicate this problem in a better way. As the article shows that DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is severe drug induced reaction which was previously known as hypersensitivity reaction .It is characterised by various signs and symptoms starting with fever in early stage followed by skin rashes or eruptions ,dermatitis ,nephritis and organ involvement mainly liver followed by kidney and lungs in middle stage finally death if untreated .
Commonly occurring symptom is fever but skin rashes ,skin eruptions and liver involvement, are the symptomatic signs of DRESS but these are also the commonly occurring symptoms for connective tissue diseases,idiopathic hypereosinophilia and viral hepatitis and these differential diagnosis of DRESS have been ruled out only in 30 % of reported cases on the basis of serology of viruses such as hepatitis A virus ,hepatitis C virus etc.
Mortality rate due to this syndrome is 10 % ,out of all culprit drugs Allopurinol is the one resulting causing severe toxic reaction called allopurinol dress syndrome which leads to increased morbidity and mortality rate and the death rate in patients with allopurinol associated DRESS is higher than other drugs described in DRESS cases .
Finally we can conclude that such syndrome should be diagnosed as soon as possible and steps should be taken to overcome or eradicate such life threatening disease, its better for a patient to receive the treatment while the illness is still in its early stage rather than making it worst .