Virus infection + sulfasalazine caused a drug reaction with a fatality rate of 10%?

*Only for medical professionals to read for reference.
If you feel unwell, seek medical advice immediately! A man has not only a viral infection, but also a drug reaction.
His life is almost dead~Case profile A 30-year-old young man has a history of fever, itchy rash and small joint pain (symmetrical involvement) in the hands and feet in the past 14 days
.

The initial diagnosis of Chikungunya fever in the local hospital [it is correct, this is the disease, Chikungunya IgM is positive, and the titer is 1:80 (reference range is 1:10)]
.

Physical examination: the patient's temperature was 38.
2℃
.

Both sides of the neck (mainly posterior triangle) and axillary lymph nodes are enlarged, accompanied by hepatosplenomegaly
.

Facial swelling and extensive measles-like rash
.

There was edema in the flexor muscles of the extremities with blisters, follicular and non-follicular pustules; the trunk, palms, soles and mucosal surfaces were not affected (Figure 1) [1]
.

The Nissl sign is not elicited
.

There is nothing special about the physical examination
.

Figure 1: Facial edema with focal suppuration and crusting (A), generalized measles-like eruption with upper extremity vesicle formation, multiple small follicles and non-follicular pustules on the trunk (B) Laboratory examination: white blood cells 26.
1×109/L↑ , Neutrophils 54%, eosinophils 21%↑, lymphocytes 17%↓, monocytes 8%, eosinophils 1.
8×109/L↑, peripheral blood smear atypical lymphocytes 14%, The erythrocyte sedimentation rate was 25 mm/h↑, alanine aminotransferase 190 IU/L↑; aspartate aminotransferase 212 IU/L↑, amylase 200 U/L and lipase 210 U/L all increased
.

Urea, electrolytes, thyroid characteristics, blood and urine cultures, antinuclear antibody serology, rheumatoid factor, viral hepatitis markers, HIV, HHV-6, chlamydia, cytomegalovirus, mycoplasma, and Ebstein-Barr virus are all negative
.

The reverse transcription polymerase chain reaction (RT-PCR) of SARS-CoV-2 in nasopharyngeal and oropharyngeal swabs was negative
.

A 4mm needle biopsy removed from the right arm showed epidermal cavernous lesions with infiltration of superficial perivascular lymphoid tissue cells
.

Chikungunya triad: fever, acute joint pain/inflammation and skin rash.
In the above cases, I saw the confusing medical term "chikungunya".
What kind of disease is it? Chikungunya fever is a mosquito-borne infectious disease caused by Chikungunya virus (CV) infection.
The main vectors are Aedes aegypti and Aedes albopictus.
It mostly occurs in summer and autumn, in tropical and subtropical regions.
Popular in the region
.

The disease has a high transmission index.
There have been multiple outbreaks in more than 100 countries and regions around the world, and the scope of the epidemic has continued to expand, causing approximately 1 million infections worldwide every year, and the epidemic areas continue to expand, and the number of cases continues to rise
.

The population is generally susceptible and may have lasting immunity after infection.
The incubation period is 2-12 days
.

CV replicates in the skin of the host bite site, spreads to skin, muscles and joints, even liver and brain tissue through viremia, and produces clinical symptoms, mainly manifested as fever, acute arthralgia/inflammation and skin rash "triad", and can be Liver damage, neurological symptoms, etc.
appear [2-3]
.

Foreign scholars [4-5] reported that decreased lymphocyte count is a typical indicator of changes in the blood of chikungunya cases, which may be due to excessive apoptosis and destruction of peripheral blood lymphocytes during viremia, especially at high viral load.
The amount of patients
.

The clinical manifestations of chikungunya fever cases are mild, with a very low case fatality rate, and no complications such as neuritis, acute myocarditis, and cardiopulmonary failure
.

There is no specific drug treatment for this disease, mainly symptomatic treatment
.

It turned out that there was more than one disease.
However, after the patients were given antipyretics, antihistamines, topical emollients and moderate corticosteroid lotions for symptomatic treatment, low-grade fever and skin rashes persisted
.

Can't help but make people wonder whether there are other diseases combined? Sure enough, further investigation of the patient revealed that he had taken sulfasalazine for 2 months to treat non-specific joint pain (the drug had been stopped for 12 days)
.

The patient has fever, skin rash, abnormal blood system, and has taken sulfasalazine.
Is it drug hypersensitivity syndrome (DIHS)? DIHS is also known as drug response with eosinophilia and systemic symptoms (DRESS).
The main clinical manifestations are skin rash, fever, abnormal blood system and internal organ damage, etc.
The incidence rate is 1/1000~1/10000, and the fatality rate is 10 %, the incubation period is 2 to 6 weeks, with an average of 3 weeks
.

Now that we consider this point, we must check it
.

The European Registry of Serious Adverse Skin Reactions (RegiSCAR) scoring system is currently the most commonly used scoring standard for diagnosing DIHS
.
The DIHS diagnostic criteria released in 2007 are as follows .

(1) Acute rash; (2) Suspected drug-induced adverse reactions; (3) Hospitalization required; (4) Body temperature ≥38.
5℃; (5) Abnormal blood tests (at least one of the following items): high lymphocytes It is above or below the reference value, eosinophils are higher than the reference value, and platelets are lower than the reference value; (6) ≥2 lymphadenopathy is present; (7) at least one internal organ is involved
.

The first 3 items must be met, and the last 4 items must meet at least 3 items
.

The RegiSCAR scoring system divides DIHS patients into 4 types: confirmed, highly suspicious, suspicious and non-DRESS
.

Table 1: Scoring system for diagnosed, highly suspicious, suspicious and non-DRESS cases of DRESS.
Note: After excluding other causes, 1 involved organ is scored 1 point, ≥2 involved organs scored 2 points; total score <2 is divided into non-DRESS, 2 ～3 is considered suspicious, 4～5 is highly suspicious, >5 is diagnosed that the patient meets fever (1 point), lymphadenopathy (1 point), atypical lymphocytes (1 point), eosinophils Hyperplasia (2 points), skin damage (1 point), liver damage (1 point), all the laboratory tests mentioned in the list are negative (1 point), the patient score is 8 points in total, and the diagnosis of DRESS is firmly established NS! Discontinuation and symptomatic supportive treatment After the diagnosis of DRESS, all non-essential drugs were immediately discontinued, and oral prednisolone (1 mg/day) was started, while corresponding supportive care was given
.

On the fourth day of treatment, the fever subsided, and the rash subsided with peeling after 10 days
.

Normal biochemistry was observed after two weeks
.

The chikungunya serological test showed positive chikungunya virus IgG
.

The dose of systemic steroid therapy was gradually reduced within 8 weeks without any signs of recurrence
.

Follow-up follow-up did not show any discomfort
.

The effective treatment further proves that the patient is indeed DRESS! When using sulfasalazine, there are rare adverse reactions to be wary of why the application of sulfasalazine will cause discomfort? ▌ The commonly used medicine for the treatment of arthritis can also cause severe allergic reactions.
Sulfasalazine is an oral compound that contains two main ingredients, sulfapyridine and 5-aminosalicylic acid
.

Due to its potential nuclear factor-κB and tumor necrosis factor-α inhibitory activity, the drug has proven to be very useful for many inflammatory diseases
.

Sulfasalazine allergy manifestations include photosensitivity and fixed drug eruption, but few studies have found that sulfasalazine allergy manifests as DRESS
.

▌ The pathological mechanism of DRESS is complicated.
The pathological mechanism of DRESS seems to be a complex interaction factor, including the culprit drugs, genetic susceptibility, comorbidities affecting drug metabolism, and temporary hypogammaglobulinemia
.

The current study also found that the reactivation of HHV-6, 7, Ebstein-Barr virus and cytomegalovirus is the cause of DRESS
.

Is CV completely "innocent"? not always! CV may be caused by DRESS by interfering with drug detoxification enzymes or by an unknown immune mechanism
.

In this regard, further research is needed to determine whether CV is the trigger of DRESS
.

▌ These drugs are also the "culprits" of DRESS.
In addition to sulfasalazine, allopurinol, aspirin, carbamazepine, hydroxychloroquine, lamotrigine, minocycline, nevirapine, olanzapine, oxcarbazepine, benzene Butazone, spironolactone, streptomycin and vancomycin can also cause DEERS
.

Learning Tips: ►DRESS is a rare drug reaction that is usually mistaken for a viral infection
.

Due to its high morbidity and 10% mortality, it is necessary to diagnose and treat as soon as possible
.

►Facial edema, eosinophilia, and multiple organ involvement make the disease different from other common medications
.

►Chikungunya virus may trigger DRESS
.

DOI:10.
1371/journal.
pone.
0186923.
[5]GodaertL,NajioullahF,BousquetL,et al.
Do two screening tools for Chikungunya virus infection that were developed among younger population work equally as well in patients aged over 65 Years? [J/OL].
PLoS Negl Trop Dis,2017,11(1):e0005256.
DOI:10.
1371/journal.
pntd.
0005256.