**4. Clinical and paraclinical characteristics of SJS/TEN**

#### **4.1 Clinical characteristics**

Stevens-Johnson syndrome and TEN develop acutely, with epidermal necrosis, mucositis at multiple sites, accompanied by systemic and other organ changes [1, 2]. In general, the first symptoms are fever, fatigue, discomfort in the upper respiratory tract, appearing a few days before skin and mucosal lesions [1, 6]. Often, it is difficult to diagnose ODSRs and predict the likelihood of progression to SJS/TEN at this stage. Many patients have EM-like lesions with atypical target lesions. However, according to Abe's study, serum granulysin levels were elevated during this time, based on which could predict the possibility of SJS/TEN [49], helping to treat early avoid complications, and reduce the risk of death.

The time from taking a suspected drug to the onset of symptoms varies widely, ranging from a few days to two months. Therefore, it is necessary to carefully review all drugs used by the patient within the previous two months, including over-thecounter drugs and dietary supplements [1].

Lesions of the ocular mucosa may precede skin lesions. Manifestations include eye discomfort, conjunctivitis, and scleritis. After a few days, the conjunctiva becomes ulcerated, oozing. Lesions on the ocular mucosa may occur concurrently with lesions of the oral mucosa and genital mucosa [1]. According to Revuz's research, 97% of SJS/TEN patients had mucosal lesions, of which, oral mucosal lesions were found in 93% of patients, ocular mucosa 78%, genital mucosa 63%, and other mucous membranes 66% [59].

Skin pain is an early symptom in SJS/TEN, the presence of which signals an epidermal necrolysis event [1]. There are many types of skin lesions with varying degrees of severity. The earliest lesions are atypical target lesions and/or itchy erythematous macules. The first sites where lesions appear are usually the upper half of the body, the head near the extremities, and the face. After that, the skin lesions spread to the rest of the body and distal extremities. Lesions on the palms and soles of the feet are quite prominent. In many patients, the first symptom is an intensely red, erythematous rash on the palms of the hands. In severe cases, the erythema may coalesce into

large macules. The skin becomes tender, vulnerable, and mild pressure can cause epidermal detachment (positive Nikolsky test). The maximum extent of skin lesions after onset is 5–7 days. Necrotic blisters appear when the necrotic epidermal detachment separates from the underlying skin [1, 59]. Extensive necrosis epidermal detachment leaves open dermis, serous exudates, susceptible to infection and bleeding (see **Figures 1**–**4**) [60].

Multiple organs are affected in SJS/TEN, with necrosis and erosion occurring in the conjunctiva, trachea, bronchi, kidneys, and intestines [52]. There have been reports of acute renal failure with increased microalbuminuria, renal tubular enzymes in the urine, demonstrating glomerular and proximal tubular damage. Lung and respiratory

#### **Figure 1.**

*A male patient with carbamazepine-induced SJS. He had erosions and dark crust on the lips, pruritic erythematous lesions on the face and the upper trunk. (photo: Tran Thi Huyen).*

#### **Figure 2.**

*A lot of blisters were formed on the dark erythematous rashes on the trunk of the patient with carbamazepineinduced SJS. (photo: Tran Thi Huyen).*

*Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis DOI: http://dx.doi.org/10.5772/intechopen.102794*

#### **Figure 3.**

*Epidermal detachments, blisters, and necrotic rashes on the trunk of a patient with allopurinol-induced TEN (photo: Tran Thi Huyen).*

lesions include tracheobronchitis, subcutaneous emphysema, dyspnea, and respiratory failure. Other systemic manifestations may include anemia, leukopenia, hepatitis, abdominal pain, diarrhea, transient elevation of liver enzymes, hypoalbuminemia, hyponatremia, and myocarditis [1].

### **4.2 Paraclinical characteristics**

#### *4.2.1 Histopathology*

The diagnosis of SJS/TEN is mainly clinical. However, skin biopsy for histopathology is necessary to further confirm the diagnosis and rule out other bullous skin diseases [1]. On histopathology, there are different degrees of epidermal lesions, the keratinocytes are necrotic individually or in plaques, forming blisters. Appendical structures such as sweat ducts and hair follicles may be affected. The dermis has an inflammatory infiltrate (mainly perivascular) of lymphocytes, histocytes, and a few eosinophils [61]. In addition, there may be liquid degeneration of the basal layer, squamous separation, and spongiosis [62]. Depending on the stage of the disease, the histopathological picture can be different. In the early stages, a histopathological picture is a group of necrotic keratinocytes with some inflammatory cells (monocytes and neutrophils). In the late and severe stages, the keratinocytes are more necrotic, the basal epithelial cells degenerate, leading to the separation of the epidermis from the dermis, the entire layers of keratinocytes of the epidermis are necrotic, only intact horny layer. In some cases, the superficial layer of the epidermis is more necrotic than the deeper layers, forming slits between the two layers of the epidermis [29]. Monocytes and neutrophils can infiltrate areas of necrosis [29, 62].

In the early stages of SJS/TEN, necrotic keratinocytes are scattered in the lower epidermis, similar to those seen in severe EM: extensive necrotic keratinocytes with vacuoles at the dermal-epidermal junction [6, 61]. When SJS/TEN is evident, the entire epidermis is necrotic, forming subepidermal bullae. Meanwhile, in severe EM, the epidermis is less necrotic, the change occurs mainly in the basal layer. The Japanese diagnostic criteria suggested that in SJS/TEN at least 10 necrotic keratinocytes were seen at 200x magnification [63]. In the superficial dermis, perivascular inflammatory infiltration and exocytosis are usually absent. In SJS/TEN, inflammation in the dermis occurs less frequently than in severe EM [61]. The degree of inflammation correlates with the disease severity, the number of infiltrating mononuclear cells in the dermis has the same prognostic value as the SCORe for TEN (SCORTEN) index to assess the severity of TEN [35].

#### *4.2.2 Microbiological tests*

Serology for diagnosis of *Mycoplasma pneumonia* [64], herpes simplex virus, Epstein-Barr virus, cytomegalovirus, ... to rule out microbial causes of mouth ulcers and skin lesions [1, 6].

#### *4.2.3 Biochemistry and hematology tests*

In SJS/TEN, the blood count may be normal or there may be disorders such as leukocytosis, leukopenia, and anemia. Many patients have a transient elevation of liver enzymes, increased urea, creatinine, blood bicarbonate, blood glucose, C-reactive protein, procalcitonin.

#### **4.3 Prognosis and complications**

#### *4.3.1 Prognostic factors*

**110** In severe cases of SJS/TEN, acute systemic disorders can lead to multi-organ failure and death. In 2000, Bastuji-Garin et al. published a valuable prognostic score for *Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis DOI: http://dx.doi.org/10.5772/intechopen.102794*


## **Table 1.**

*SCORTEN score for Stevens-Johnson syndrome/toxic epidermal necrolysis and risk of in-hospital mortality based on the SCORTEN [1, 65].*

SJS/TEN, called SCORTEN, which used seven clinical factors to predict in-hospital mortality. Each factor is worth one point, the higher the total score, the higher the risk of death [65]. Several studies have shown a gradual increase in SCORTEN scores during patient hospitalization, with a significant change observed on day 1 and day 4 (see **Table 1**) [66].

### *4.3.2 Complications*

It is a disease with a high risk of death, but with time management and treatment, SJS/TEN can be cured. However, it is necessary to note visceral complications (liver, kidney) [52], eye complications, nail disorders [67], skin pigmentation changes after the disease as well as the psychological trauma of the patient. Among them, eye complications are noted the most, with different degrees [68]. Mild degree with eyelid edema, conjunctivitis; a moderate degree of membranous conjunctivitis, corneal epithelial loss, corneal ulceration, corneal infiltrates; in severe cases, there is the irreversible loss of corneal epithelium, loss of vision [1, 68, 69].
