Constitutional signs of fever, fatigue, coughing, and sore throat may be observed several days before cutaneous signs develop among patients with SJS. The following signs and symptoms are seen among patients suffering from SJS:

• Skin pain
• Facial swelling
• Tongue swelling
• Reddish rash
• Hives
• Blisters on the skin and mucous membrane
• Skin sloughing or shedding

• Pain

  By the time she left the hospital, her eyes were severely light sensitive and she was in constant pain, making returning to work and college impossible... [bostonsight.org]

  They are extremely painful and limit oral intake. The teenager was apathetic, mildly dehydrated, and appeared to be in pain. [web.archive.org]

  Before the skin symptoms start, many people report feeling generally unwell with a headache and joint pain, accompanied by a cough. The main feature of Stevens-Johnson syndrome is a skin rash. [gosh.nhs.uk]

  […] by lighter areas are considered diagnostic of SJS Painful red or purplish rash, blisters on the skin, mouth, eyes, ears, nose and genital area. [medindia.net]

• Fever

  However, fever should be treated with antipyretic medication as needed. [journals.lww.com]

  High fever occurs in these conditions, frequently before the skin and/or mucosa is affected. [ncbi.nlm.nih.gov]

  The fever which preceded the appearance of the rash was most probably due to viral infection since her son was suffering from fever and flu like symptoms. [web.archive.org]

• Malaise

  SJS/TEN manifest with an "influenza-like" prodromal phase (malaise, fever), followed by painful cutaneous and mucous membrane (ocular, oral, and genital) lesions, and other systemic symptoms. [ncbi.nlm.nih.gov]

  Discontinue Isentress and other suspect agents immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or [mnn.com]

  According to a 2011 paper in the "Expert Review of Clinical Immunology," the earliest signs of Stevens-Johnson Syndrome, or SJS, are often fever and malaise, a vague feeling of body discomfort, such as achy joints and generalized soreness. [livestrong.com]

  Patients may present with fever, malaise, myalgia and ocular manifestations. Mortality has been estimated at 5% of cases (3, 4). From 1973, to 2005, Health Canada received 4 reports of SJS suspected of being associated with ibuprofen. [apps.who.int]

• High Fever

  High fever occurs in these conditions, frequently before the skin and/or mucosa is affected. [ncbi.nlm.nih.gov]

  – In many cases preceded with flu like symptoms and high fever. – As it evolves the skin literally sloughs off. – Ocular involvement includes severe conjunctivis, iritis, palpebral edema, conjunctival and corneal blisters and erosions, and corneal perforation [sjsupport.org]

  High fever is a constant feature. Visceral manifestations are also frequent with hematological, respiratory and digestive involvement. Etiology In two thirds of cases, TEN is triggered by a clearly identifiable drug allergy. [orpha.net]

• Fatigue

  SJS and TEN are life threatening and complications can include permanent blindness, lung damage, chronic obstructive pulmonary disease (COPD), scarring of mucous membranes, and chronic fatigue syndrome, among others; and, WHEREAS, The individuals, families [michigan.gov]

  Novel physical sequelae included chronic fatigue (76%) and pruritus (53%). [ncbi.nlm.nih.gov]

  Fatigue Some victims of Stevens johnson syndrome and toxic epidermal necrolyssis (lyell syndrome) complain about phases of intense fatigue, or even great weariness. Cardiac unrests Tachychardia. Blood unrests Leukopenia, Thrombopenia. [avimedi.net]

  Discontinue Isentress and other suspect agents immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or [mnn.com]

  Constitutional signs of fever, fatigue, coughing, and sore throat may be observed several days before cutaneous signs develop among patients with SJS. [symptoma.com]

• Cough

  The cough is typically a dry, nonproductive cough arising from increasingly irritated membranes in the airway and lungs. [livestrong.com]

  Both Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis often start with symptoms such as cough, aching, headaches, a burning sensation in the eyes or fever. [aaaai.org]

  Sometimes the mucous membranes of the digestive and respiratory tracts are involved, resulting in diarrhea and cough, pneumonia, and difficulty breathing. [merck.com]

• Dyspnea

  A 27-year-old female developed progressive dyspnea after SJS induced by taking amoxicillin at the age of 10. Finally, she died of exacerbation of type II respiratory failure after 17 years from clinically diagnosed as having BO. [ncbi.nlm.nih.gov]

  Bronchial epithelium may also slough, causing cough, dyspnea, pneumonia, pulmonary edema, and hypoxemia. Glomerulonephritis and hepatitis may develop. [merckmanuals.com]

  […] experiencing a cold epidemic with rhinorrhea, dry cough and mild wheezing and she said her health deteriorated progressively, with headache, earache, pain on swallowing, nausea without vomiting, constipation, pleuritic-type bilateral chest pain, and slight dyspnea [archbronconeumol.org]

• Rhinorrhea

  For five days before admission, the patient´s family had been experiencing a cold epidemic with rhinorrhea, dry cough and mild wheezing and she said her health deteriorated progressively, with headache, earache, pain on swallowing, nausea without vomiting [archbronconeumol.org]

  After an incubation period of 1 to 4 weeks, the infection typically presents with cough, pharyngitis, and rhinorrhea. Only 10% of patients develop pneumonia [4]. [hindawi.com]

  Symptoms and signs of mucous membrane involvement include blood-streaked rhinorrhea, conjunctival injection, hemorrhagic crusting of the lips, burning on urination, pain on defecation, and oral and genital erosions. [clinicaladvisor.com]

• Tachypnea

  A prodrome of chills is followed by pharyngitis, headache, tachypnea, and tachycardia. In several days, bullous mucosal lesions develop, especially in the oropharynx. [aao.org]

• Abdominal Pain

  […] of the skin 90% Abnormality of temperature regulation 90% Acantholysis 90% Hypermelanotic macule 90% Malabsorption 90% Nausea and vomiting 90% Weight loss 90% Abnormality of neutrophils 50% Excessive salivation 50% Feeding difficulties in infancy 50% Abdominal [web.archive.org]

  pain Pain in stomach Stomach pain [ more ] 0002027 Elevated erythrocyte sedimentation rate High ESR 0003565 Nephropathy 0000112 Nephrotic syndrome 0000100 Renal amyloidosis 0001917 Urticaria Hives 0001025 5%-29% of people have these symptoms Abnormal [rarediseases.info.nih.gov]

• Oral Ulcers

  TREATMENT: Oral ulcers had been topically treated with an oral balance gel. Intravenous injection of immunoglobulin was then applied and the patient was discharged after 5 days of treatment with the total symptoms in remission. [ncbi.nlm.nih.gov]

  Oropharyngeal (mouth) lesions may be so intolerable as to prevent eating, and there may be recurring oral ulcers. Often, the skin lesions may look like a target-lesion (3 concentric zones of color change) or as bullae (bubble-like). [healthcentral.com]

  Physical examination revealed injection of the conjunctivae with sticky yellow discharge, swollen lips with erosion of the mucosa, hemorrhagic crusting, intraoral ulcers, dry oral mucous membranes, ulceration of the head of the penis, and a generalized [web.archive.org]

  The mucous membranes are also characteristically affected and the patient presents with oral ulcers, genital ulcers, and/or severe conjunctivitis. When > 30% of the skin is affected, the condition is referred to as toxic epidermal necrolysis (TEN). [amboss.com]

• Sore Mouth

  […] days after blisters form If you have Stevens-Johnson syndrome, several days before the rash develops you may experience: Fever Sore mouth and throat Fatigue Cough Burning eyes When to see a doctor Stevens-Johnson syndrome requires immediate medical attention [mayoclinic.org]

  The initial signs of SJS are bloody crusts on the lips, a sore mouth that has a foul smell, and purple-red tender spots on the skin. Drinking and eating are difficult, and light is painful to the eyes. [childrensclinicofraceland.com]

• Lip Blisters

  blisters and peels off in waves. [nbcnews.com]

• Aphthous Stomatitis

  stomatitis Recurrent canker sores 0011107 Restrictive ventilatory defect Stiff lung or chest wall causing decreased lung volume 0002091 Short stature Decreased body height Small stature [ more ] 0004322 Vasculitis Inflammation of blood vessel 0002633 [rarediseases.info.nih.gov]

• Hypertension

  Most common side effects associated with long-term cyclosporin treatment such as hypertension and renal toxicity are not seen in treatment with short duration of treatment. [ijdvl.com]

  His medical history includes type 2 diabetes, hypertension, obesity, and gout. You consider whether this patient might have Stevens-Johnson syndrome (SJS) or erythema multiforme majus (EMM). [doi.org]

  Human immune deficiency virus was co-mentioned in a total of 116 documents on SJS and TEN while cancer was co-mentioned in 91, tuberculosis in 29, hypertension in 19, and diabetes mellitus in 16 documents. [ojrd.biomedcentral.com]

• Arthralgia

  Description A syndrome characterized by severe erythema multiforme-like eruption of the skin and lesions of the oral, genital and anal mucosa, and haemorrhagic crusting on the lips, associated with fever, headache and arthralgia. [web.archive.org]

  Complications can include hepatitis, nephritis, gastrointestinal bleeding, pneumonia, arthritis, arthralgia, fever, and myalgia. [rxlist.com]

  Heilwart Joseph Victor Klauder Noël Fiessinger A syndrome characterized by severe erythema multiforme-like eruption of the skin and lesions of the oral, genital and anal mucosa, and haemorrhagic crusting on the lips, associated with fever, headache and arthralgia [whonamedit.com]

• Photophobia

  Ocular symptoms: painful red eye, purulent conjunctivitis, photophobia, blepharitis. Signs General examination: fever, tachycardia, hypotension; altered level of consciousness, seizures, coma. [patient.info]

  All these patients had photophobia. Visual acuity improved in all these patients with ScCL wear. [ncbi.nlm.nih.gov]

  Lesions are painful and lead to hypersalivation, feeding problems, photophobia, and burns following urination. High fever is a constant feature. Visceral manifestations are also frequent with hematological, respiratory and digestive involvement. [orpha.net]

• Anterior Uveitis

  Eye complications: include corneal ulceration and anterior uveitis. Sight impairment may develop secondary to severe keratitis or panophthalmitis in 3-10% of patients. Vaginal stenosis and penile scarring have been reported. [patient.info]

  At least 2 mucosal surfaces are affected including: Eyes (conjunctivitis, less often corneal ulceration, anterior uveitis, panophthalmitis) — red, sore, sticky, photosensitive eyes Lips/mouth (cheilitis, stomatitis ) — red crusted lips, painful mouth [dermnetnz.org]

• Conjunctival Injection

  High fevers and cold symptoms are present and two or more mucosa are involved, with corresponding symptoms: conjunctival injection, photophobia, odynophagia, pruritus, dysuria, etc. [archbronconeumol.org]

  External photograph of the left eye showing a corneal epithelial defect and diffuse conjunctival injection Figure 2. Eversion of the right upper eyelid shows a conjunctival membrane. [webeye.ophth.uiowa.edu]

  Symptoms and signs of mucous membrane involvement include blood-streaked rhinorrhea, conjunctival injection, hemorrhagic crusting of the lips, burning on urination, pain on defecation, and oral and genital erosions. [clinicaladvisor.com]

  SJS-TEN overlap: note purulent discharge and oral erosions; crusting at the eyelid margins with conjunctival injection Figure 2. [pulmonologyadvisor.com]

• Blister

  The syndrome is characterized by generalized macular lesions that rapidly spread and consolidate leading to epidermal necrosis, blistering and epithelial sloughing. [symptoma.com]

  The areas of rash enlarge and spread, often forming blisters in their center. The skin of the blisters is very loose and easy to rub off, often with just a gentle touch or pull, and the blisters peel off over a period of 1 to 3 days. [merck.com]

  It results in a severe rash and blistering of the skin and mouth, and could include symptoms such as: Rash, blisters or red spots on the skin Blisters in the mouth, eyes, ears, nose or genital area Swelling of the eyelids Fever or flu-like symptoms In [youhavealawyer.com]

  Rarely does the skin develop blisters in the early stages of SJS skin rash. The rash may also arise in the form of sores around the mouth. Later, the skin may develop blisters and will begin to detach and slough off. [livestrong.com]

• Skin Rash

  A 41-year-old female presented with a skin rash and abnormal liver function tests after the recent initiation of fluoxetine. Skin and liver biopsies showed features of SJS and DILI, respectively. [ncbi.nlm.nih.gov]

  A widespread skin rash of irregularly shaped, flat, purplish red spots also develops, which may be painful. The skin rash may develop on any part of the body but often begins on the face, neck, chin, and trunk. [myhealth.alberta.ca]

  After the onset of the earliest SJS symptoms, a red or purple skin rash develops and will slowly spread and worsen over the course of hours to days. Rarely does the skin develop blisters in the early stages of SJS skin rash. [livestrong.com]

• Alopecia

  Hair loss (alopecia). Dryness of mucus membranes, which could cause problems urinating. Chronic fatigue syndrome. Difficulties with your sense of taste. [my.clevelandclinic.org]

  Among people who survive, long-term effects of SJS/TEN can include changes in skin coloring (pigmentation), dryness of the skin and mucous membranes (xerosis), excess sweating (hyperhidrosis), hair loss (alopecia), and abnormal growth or loss of the fingernails [web.archive.org]

  […] include the following: Postinflammatory dyspigmentation (hyperpigmentation or hypopigmentation) Abnormal scarring Eruptive nevi Nail changes (onychomadesis, anonychia, pterygium formation, ridging, dystrophy, abnormal pigmentation) Telogen effluvium Alopecia [emedicine.com]

• Eczema

  Eczema marginatum. In: Virchow’s Handbuch der speciellen Pathologie und Therapie. Erlangen, 1860, 1, 1 Abt., pp. 361-363. E. Fuchs: Herpes oris conjunctivae. Klinische Monatsblätter für Augenheilkunde, Stuttgart, 1876, 14: 333-351. R. [web.archive.org]

  The most common are chickenpox, herpes, impetigo, and a form of eczema called dyshidrosis. [en.wikipedia.org]

  Seborrheic eczema. Saunders-Elsevier. 2010. pp. 694-6. (This book evaluates the evidence for treatments for many different diseases of the skin. [pulmonologyadvisor.com]

• Epistaxis

  Clinical Presentation The following signs may be noted on examination: • Fever • Tachycardia • Hypotension • Altered level of consciousness • Epistaxis • Conjunctivitis • Corneal ulcerations • Erosive vulvovaginitis or balanitis • Seizures • Coma 28. [slideshare.net]

  In post-marketing experience, as with other azole antifungals, bleeding events (bruising, epistaxis, gastrointestinal bleeding, haematuria and melena) have been reported, in association with increases in prothrombin time in patients receiving fluconazole [web.archive.org]

• Hematuria

  Twenty patients (61%) complained of dysuria and one child had gross hematuria in the setting of meatal lesion. Petroleum jelly was used in the majority of patients. [ncbi.nlm.nih.gov]

  Complications include: Blindness Pneumonitis (inflammation of the lungs) Myocarditis (inflammation of the muscles in the heart) Hepatitis Hematuria (blood in the urine) Kidney failure Sepsis (blood infection) Death Please consult your physician before [brownandcrouppen.com]

  Complete metabolic panel Elevated aspartate aminotransferase and/or alanine transaminase may be seen Elevated glucose Elevated blood urea nitrogen and creatinine Decreased bicarbonate indicating metabolic acidosis Urinalysis Proteinuria Microscopic hematuria [pulmonologyadvisor.com]

  Hematuria and proteinuria may be seen indicating renal involvement. Blood urea nitrogen and serum creatinine levels may be raised because of dehydration. Serum electrolyte levels may guide fluid and electrolyte administration. [ijdvl.com]

• Headache

  Both Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis often start with symptoms such as cough, aching, headaches, a burning sensation in the eyes or fever. [aaaai.org]

  Description A syndrome characterized by severe erythema multiforme-like eruption of the skin and lesions of the oral, genital and anal mucosa, and haemorrhagic crusting on the lips, associated with fever, headache and arthralgia. [web.archive.org]

  The case presented in this report is that of a 17-year-old female who presented to her primary care provider with a chief complaint of headache; she was initially diagnosed with a urinary tract infection and prescribed nitrofurantoin (Macrobid). [ncbi.nlm.nih.gov]

  JOINT PAINS Several victims of stevens johnson syndrome / lyell syndrome complain of joint pains HEADACHES Some victims of stevens johnson syndrome / lyell syndrome complain of headaches, cephalalgy. [avimedi.net]

• Seizure

  Long Term use of Dilantin to treat seizure disorders and epilepsy. Dilantin can accumulate in the cerebellar cortex over long periods of time which can cause atrophy of the cerebellum. [stevens-johnsonsyndrome.org]

  Here we show that there is a strong association in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and Stevens-Johnson syndrome induced by carbamazepine, a drug commonly prescribed for the treatment of seizures. [ncbi.nlm.nih.gov]

  If you have a gene called HLA-B 1502, you have an increased risk of Stevens-Johnson syndrome, particularly if you take certain drugs for seizures, gout or mental illness. [mayoclinic.org]

• Altered Mental Status

  mental status, worsening glucose control, etc. [pulmonologyadvisor.com]

Patients are systematically examined physically for the eminent cutaneous lesion and associated signs of SJS. A detailed clinical history on the onset of the symptomatology will easily grasp the diagnosis for SJS. A skin biopsy is frequently done to definitively diagnose SJS in suspected patients.

The most important approach in the treatment of SJS is the sudden discontinuation of the inciting factor implicated in the initiation of the immune response. In cases where the inciting drug is not identified, physicians will usually ask their patients to discontinue all non-essential drugs to eliminate the possible causative agent. SJS is a medical emergency, thus all patients are managed promptly in the hospital to stabilize fluid imbalance and correct nutritional deficiencies. Adequate wound care and eye care may be in place where another specialist may be brought in for comanagement [9].

Antiinflammatory agents to control inflammation, itching, and pain may be used to allay these symptoms. Corticosteroid may also be given as an immune modulator agent for SJS [10]. Patients are given antibiotic therapy to control concurrent infections associated with the cutaneous disease.

Cutaneous lesion of mild SJS typically heals within 1 to 2 weeks from onset without any serious sequelae. However, this may be complicated by secondary skin infections that increases the morbidity rates among afflicted patients. The mortality rate in SJS varies directly with the body surface area (BSA) of the cutaneous sloughing. Mortality rates may climb beyond 50% for BSA percentage of 25% to 35% of skin affected [8]. Patients who survive SJS may develop a number of sequelae in some cases, these include photophobia, watery eyes, inverted eyelashes, and burning sensation of the eyes.

In more than half the cases of SJS, drugs are commonly considered as the precipitating agent. The following are the most common drugs in the development of the severe cutaneous reaction in SJS:

• Sulfa drugs (sulfasalazine and cotrimoxazole) [2]
• Antibiotics (amoxicillin, ampicillin and fluoroquinolones)
• Anticonvulsant agents (phenytoim, carbamazepine, and phenobarbital)
• Other drugs (piroxicam and allopurinol)

There are other factors that may incite the hypersensitivity reaction in SJS, these are infections (most commonly by Mycoplasma pneumonia), Graft rejection disease, and vaccination reactions. Studies have demonstrated that patients with systemic lupus erythematosus (SLE) have an increased risk in developing SJS [3]. In some instances, the true etiology of SJS remains unknown or idiopathic in nature.

In the United States, medic aid data has determined that the incidence of SJS has reached to 6.8 cases per million population per annum [4]. The majority of cases of SJS have a predilection to the winter and early spring seasons. Sulfonamides and piroxicam are the most common inciting factors implicated in the US, while allopurinol is more common in Southeast Asian nations like Malaysia and Hong Kong. SJS occurs in all races but is more commonly seen in the white races compared to their dark skinned counterparts. Large cohort studies have determined that the mean age of onset in SJS is 25 years old and this may occur in children as young as 3 years old.

The pathophysiology in SJS is described as an idiosyncratic and delayed hypersensitivity reaction to an inciting factor. There are certain sectors of the population who are more prone to the disease inclusive are those in immunocompromised states (i.e. AIDS) and those under radiotherapy for cancer [5]. The antigen presentation and the production of acute phase reactants (like tumor necrosis factor) by the tissue dendrocytes will advertently result in the recruitment and the proliferation of the T-lymphocytes which enhances cytotoxicity [6].

There is a subsequent death in the keratocytes that leads to the separation of the dermis and the epidermis that clinically present as sloughing. The perpetuation of the inflammation by the chemokines leads to extensive epidermal necrolysis of the surface epithelium [7]. Inciting factors may be discontinued to stop and reduce the inflammatory process or may be titrated in smaller divided doses if drug is absolutely necessary and essential.

Patients who have Asian lineage are perpetually advised to undergo genetic testing for SJS before starting on carbamazepine indicated for the control epilepsy. Patients who have had SJS in the past must avoid by all means to take in the identified inciting agent to avoid its recurrence. In the same way, family members are also discouraged to ingest the inciting drug because of the genetic risk factors involved.

Steven-Johnson syndrome (SJS) is a rare and life-threatening disorder of the skin and the mucous membrane [1]. This syndrome is usually a reaction to an infection or an intake of a medication that starts out as a reddish rash that disseminates in the skin surface and forms blisters. SJS is considered as a medical emergency that requires prompt treatment focusing on the elimination of the causative agent, the control of the symptoms, and preventing further complications.

Definition

Steven-Johnson syndrome is a rare and life-threatening disorder of the skin and the mucous membrane described to exaggerated hypersensitivity response to an inciting factor.

Cause

More than half the cases of SJS are initiated by the intake of drugs like sulfa drugs, antibiotics, anticonvulsants, and analgesics. Less common causes includes infections, graft rejection reactions and vaccinations.

Symptoms

Patients will present with severe skin and mucous membrane lesions which are erythematous, itchy, and blistering.

Diagnosis

A detailed clinical history and a meticulous physical examination of the skin may secure the diagnosis of SJS. Skin biopsy is the definitive test used for this kind of disease.

Treatment and follow-up

Treatment focuses on the prompt removal of the inciting factor, the stabilization of the patient through fluid resuscitation, and the control of the signs and symptoms.

1. French LE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our current understanding. Allergol Int. Mar 2006; 55(1):9-16.
2. Fernando SL, Broadfoot AJ. Prevention of severe cutaneous adverse drug reactions: the emerging value of pharmacogenetic screening. CMAJ. Mar 23 2010; 182(5):476-80.
3. Horne NS, Narayan AR, Young RM, Frieri M. Toxic epidermal necrolysis in systemic lupus erythematosus.Autoimmun Rev. Feb 2006;5(2):160-4.
4. Strom BL, Carson JL, Halpern AC, et al. A population-based study of Stevens-Johnson syndrome. Incidence and antecedent drug exposures. Arch Dermatol. Jun 1991; 127(6):831-8.
5. Rotunda A, Hirsch RJ, Scheinfeld N, Weinberg JM. Severe cutaneous reactions associated with the use of human immunodeficiency virus medications. Acta Derm Venereol. 2003; 83(1):1-9.
6. De Rojas MV, Dart JK, Saw VP. The natural history of Stevens Johnson syndrome: patterns of chronic ocular disease and the role of systemic immunosuppressive therapy. Br J Ophthalmol. Aug 2007; 91(8):1048-53.
7. French LE, Trent JT, Kerdel FA. Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson syndrome: our current understanding. Int Immunopharmacol. Apr 2006; 6(4):543-9.
8. Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. Aug 2000; 115(2):149-53.
9. Inachi S, Mizutani H, Shimizu M. Epidermal apoptotic cell death in erythema multiforme and Stevens-Johnson syndrome. Contribution of perforin-positive cell infiltration. Arch Dermatol. Jul 1997; 133(7):845-9.
10. Paquet P, Paquet F, Al Saleh W, Reper P, Vanderkelen A, Piérard GE. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. Am J Dermatopathol. Oct 2000; 22(5):413-7.