Answers

Short answers

1 This patient has erythema multiforme, which is characterised by a maculopapular rash made of multiple round "bull’s eye" target shaped lesions.

2 Mycoplasma pneumoniae is the infectious agent most likely to be responsible for both extensive community acquired pneumonia and erythema multiforme.

3 The key to diagnosis is serological testing.

4 Severe community acquired pneumonia that results in acute respiratory failure with persisting deep hypoxaemia should be managed in an intensive care unit. Treatment should entail early intravenous administration of an empirical antibiotic regimen comprising broad spectrum β-lactam and a macrolide.

Long answers
1 Diagnosis of the skin rash
The term "erythema multiforme" is used to describe a special category of maculopapular rash that encompasses a wide range of different morphologic types (including plaques, vesicles, and bullae), which can occur concurrently. Rashes of this nature occur as a reaction to an infection or to medication (box 1);¹ in more than 50% of cases, however, no underlying cause is found.

Box 1 Main causes of erythema multiforme (in order of incidence) Infections Herpes simplex virus 1 and 2 M pneumoniae Fungal infections Medications Barbiturates Hydantoin Non-steroidal anti-inflammatory drugs (NSAIDs) Penicillins Phenothiazines Sulfonamides, including hypoglycaemics

Erythema multiforme lesions are characterised by a central erythema surrounded by a narrow ring of normal appearing skin that is in turn surrounded by another thin ring of erythema to form target-like lesions ("iris" or "bull’s eye" appearance; shown in fig 2). ²

View larger version (3259K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2 A classic "bull’s eye" target shaped lesion (arrow) in a patient with erythema multiforme

 
Lesions can be symmetrically or asymmetrically distributed on the trunk and extremities and show a predilection for knees, elbows, palms, and soles. A skin biopsy is not necessary when the clinical picture is clear because biopsy findings are not specific for erythema multiforme. Mucosal involvement can be present and can vary in degree from oral blisters and erosions to haemorrhagic conjunctivitis and stomatitis. When a patient with erythema multiforme presents in a serious clinical condition with severe mucosal erosions, the terms Stevens-Johnson syndrome or erythema multiforme major are used. Our patient’s lesions rapidly fused together to produce large red oozing areas that spread to the whole skin surface. No desquamation was noted.

2 Suspected pathogen responsible for the community acquired pneumonia
The agent responsible for community acquired pneumonia cannot be accurately predicted from a patient’s clinical features. The importance of this point has been underlined by the British Thoracic Society in its latest guidelines for the management of community acquired pneumonia in adults.³ Keeping this consideration in mind, very few infectious agents are actually capable of causing both community acquired pneumonia and erythema multiforme in an immunocompetent human adult. Viral or atypical bacterial pathogens such as M pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, and Coxiella burnetii should be considered first. Among the many possible associations between erythema multiforme and infectious diseases, the association with M pneumoniae infection is by far the most common in patients with pneumonia.² M pneumoniae is believed to account for 15-20% of all pneumonias and is one of the leading pathogens responsible for community acquired pneumonia in young adults.⁴ M pneumoniae pneumonia is often considered the paradigm of the term "walking pneumonia", which is used to describe the gradual onset of symptoms in this disorder relative to the often acute presentation of respiratory infection seen in patients infected with Streptococcus pneumoniae or a virus. Interestingly, the present case emphasizes that M pneumoniae might also come in the form of a fulminant life threatening pneumonia.^{5 6}

3 Confirming the diagnosis
Unfortunately, diagnosis is often delayed and retrospective in patients with pneumonia caused by atypical pathogens because of the lack of a rapid, accurate, and widely available diagnostic test. Bedside testing for cold agglutination—which is the result of a non-specific early IgM reaction against an altered I antigen on the surface of erythrocytes—supports the diagnosis in about 50% of adult patients.⁷ The complement fixation test is the serological technique most commonly used to detect M pneumoniae infection, but raised titres can usually only be detected 10-14 days after the onset of the disease. Rapid identification of M pneumoniae in respiratory secretions by using molecular techniques, such as polymerase chain reaction, can provide a diagnosis within a few hours in some cases. Although not available in many centres, polymerase chain reaction is emerging as one of the most accurate methods for the rapid identification of atypical respiratory pathogens.⁸ In the present patient, diagnosis of M pneumoniae infection was confirmed by testing serum samples for the presence of IgM antibodies specific for M pneumoniae. The antibodies were in a titre of 1:40 at the time of admission to the hospital and in a titre of 1:1280 10 days later.

4 Management
In patients diagnosed with community acquired pneumonia, antimicrobial treatment should be started promptly within the first hours of arrival to the hospital.⁹ This approach is particularly important in individuals with M pneumoniae pneumonia, in whom a delay in the administration of appropriate antibiotics can worsen the severity of the disease.¹⁰ Severity assessment and age are essential in predicting prognosis and, in turn, determining management and the choice and administration method of antibiotic treatment. The severity scoring system recommended in Europe is a simple five point scale called CURB-65 (box 2). Patients with a CURB-65 score of three or more are at high risk of death and should be managed in hospital as having severe community acquired pneumonia.^{11 12} Those patients with a score of two are at increased risk of death and should be considered for short stay inpatient treatment, and those with a score of zero or one are at low risk of death and should be treated at home.

Box 2 The CURB-65 score for assessing the severity of community acquired pneumonia11 Confusion (new onset mental confusion) Urea (>7 mmol/l) Respiratory rate (>30 breaths/min) Blood pressure (low systolic (<90 mm Hg) or diastolic (60 mm Hg)) 65 (age 65) One point for each item in the list

Severe community acquired pneumonia should be treated with an intravenous combination of a broad spectrum β-lactam, such as co-amoxiclav, or a third generation cephalosporin; and a macrolide or a fluoroquinolone. The decision to admit such a patient to an intensive care unit is a matter of clinical judgment and depends on the severity and evolution of the disease. The Infectious Diseases Society of America and the American Thoracic Society have both recently produced guidelines to determine whether a patient should be admitted to an intensive care unit.¹³ These major and minor criteria have now been validated and are shown in box 3.¹⁴

Box 3 Validated criteria to determine admission to an intensive care unit for a patient with severe community acquired pneumonia12 13    Minor criteria Respiratory rate 30 breaths/minute PaO2/FiO2 250 Multilobar infiltrates Confusion and/or disorientation Uraemia (BUN level 20 mg/dl) Leukopenia (WBC 4x109 cells/l) Thrombocytopenia (platelet count 100x109 cells/l) Hypothermia (core temperature <36°C) Hypotension (SBP <90 mmHg; requiring aggressive fluid resuscitation)    Major criteria Receipt of invasive mechanical ventilation Septic shock with the need for vasopressors Patients with one major criterion or three minor criteria should be admitted to an intensive care unit. Abbreviations: BUN, blood urea nitrogen; PaO2/FiO2, ratio of arterial oxygen tension to inspired oxygen fraction; SBP, systolic blood pressure; WBC, white blood cell count.

Direct admission to an intensive care unit is necessary for patients with septic shock who require vasopressors and for individuals with acute respiratory failure who require intubation and mechanical ventilation (major criteria). Direct admission to an intensive care unit is recommended for patients with three of the minor criteria for severe community acquired pneumonia. The case patient was rapidly admitted to our intensive care unit because of acute respiratory failure (tachypnoea and cyanosis) and acute lung injury, as shown by extensive dense bilateral infiltrates on the chest radiograph and refractory hypoxaemia (PaO₂/FiO₂ <300).¹⁵ He required noninvasive mechanical ventilation for four days and was discharged to a respiratory ward on the fifth day. The patient recovered well and went back home without any sequelae.

Cite this as: BMJ 2009;338:b1604