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Mycoplasma pneumoniae associated with Stevens Johnson syndrome.

SUMMARY

We describe a case of Mycoplasma pneumoniae chest infection associated with Stevens Johnson syndrome. The patient had extensive epidermal bullous vesicles, oropharyngeal and genital ulceration and required prolonged ventilation due to respiratory failure. Mycoplasma pneumoniae infections are often asymptomatic but can involve multiple organ systems. Respiratory tract involvement is generally benign though 3 to 10% of patients develop clinical pneumonia. Secondary skin reactions are common (20 to 25%), although few patients infected develop Stevens Johnson syndrome. It has been suggested that Mycoplasma pneumoniae may be the most common infectious cause of Stevens Johnson syndrome.

Key Words: Mycoplasma pneumoniae, Stevens Johnson syndrome, atypical pneumonia, erythema multiforme

CASE HISTORY

A 23-year-old Caucasian male was admitted to hospital with dyspnoea, fever and productive cough. He had been 'backpacking' in far North Queensland, Australia, for seven weeks and had recently visited New Zealand, Fiji and the United States. He had been unwell for three weeks with a dry cough, sore throat, fever and malaise. Three days prior to admission the patient was seen by a general practitioner and was prescribed a course of amoxicillin.

On the day of admission he presented to a regional hospital with worsening fevers, cough, dyspnoea and an extensive rash over his upper body with ulceration of his oral mucosa. Given his condition, he was transferred to the Tweed Hospital for further investigation and ongoing management. On physical examination he was dyspnoeic and distressed due to facial and mouth pain. His temperature was 39.0[degrees]C, heart rate was 96 beats per minute, respiratory rate was 34 breaths per minute, with a blood pressure of 135/56 mmHg. His pulse oximetry saturation was 95% on 10 1/min oxygen and decreased quickly to 85% on 31. Auscultation demonstrated crackles at the base of his right lunglield with poor air entry and widespread wheeze. He had a generalised vesicular rash, numerous bullous vesicles on his chest and upper limbs (Figure 1), with extensive ulceration of his oropharynx and stomatitis. There was no conjunctival involvement and apart from urethral mucosal ulceration, the rest of the physical examination was unremarkable.

[FIGURE 1 OMITTED]

Laboratory examination demonstrated a normal white cell count (WCC) with raised neutrophils and reduced lymphocytes (8.0X[10.sup.9]/1 and 0.6X[10.sup.9]/1 respectively). The haemoglobin concentration was 13.9 g/dl and platelet count was 235,000/bk1. His renal and liver function tests were normal and his C-reactive protein was 100.7 mg/1. Serology was requested including HIV, Mehoidosis, Legionella, Herpes simplex virus 1 and 2, Varicella, Influenza (A and B), respiratory syncytial virus, Chlamydia, Adenovirus and Parainfluenza (1, 2 and 3). Swabs were taken from the facial and genital ulcerations for microscopy, culture and sensitivity (MCS), sexually transmissible disease screening, and vesicular fluid sent for polymerase chain reaction (PCR) studies for Herpes simplex and Varicella zoster. Sputum was collected and sent for MCS. A chest X-ray showed right lower lobe consolidation, increased markings posterior to the heart and no pneumothorax. He was admitted to the general ward and treated for community-acquired pneumonia with a presumptive drug eruption rash. He was given intravenous meropenem and azithromycin, oral prednisolone, salbutamol nebulisers and supplementary oxygen. The intensive care unit (ICU) was notified for possible airway compromise; however admission was declined with close regular review.

On day two the patient continued to be unwell with increasing dyspnoea, decreasing saturations and increasing oxygen requirements. The epidermal bullae were increasing in size and the oral ulcerations were extremely painful, making it difficult to swallow secretions and sputum. A high resolution computed tomography chest scan showed bibasal consolidation consistent with infection but with no specific patterns. Serology returned strongly positive for Mycoplasma pneumoniae (MP) antibodies with titres of 640 (1:640 dilution). Other investigations were within the normal range. A skin biopsy was not performed and the condition was diagnosed as Stevens Johnson syndrome secondary to MP. Interestingly, one of the patient's travelling companions also had upper respiratory tract infection symptoms, had high titres for MP and was treated with oral azithromycin by her local doctor without complication.

The patient was again reviewed by the ICU, noted to be tiring, uncomfortable and with saturations of 90% on 101/min humidified oxygen. He was transferred to the ICU for a trial of nasal continuous positive airway pressure, which was poorly tolerated and commenced on bi-level positive airway pressure. This maintained saturations above 95% overnight, however his work of breathing increased and he appeared tired and anxious on the morning round.

He was intubated and ventilated on day three. Fibreoptic bronchoscopy was performed demonstrating copious purulent sections from both bronchi. Washings returned positive for MP further confirming the pathogenesis of his chest infection. His chest roentgenogram was consistent with acute respiratory distress syndrome. The course was complicated by bilateral pneumothoraces secondary to high pressure requirements and intercostalchest drains were inserted (20 cm[H.sub.2]0 of suction). His oxygen requirements improved over the following days from an inspired oxygen fraction of 1.0 to 0.35. He failed extubation on day 11, was tracheotomised and ventilated for a further four days. He was weaned off ventilation, transferred to a heat and moisture exchanger on 2 1 /min oxygen on day 15 and was decannulated on day 17.

His skin showed considerable improvement during the admission. Many vesicles coalesced, ruptured and desquamated. Others crusted over without eruption. No lesions developed secondary infection.

He was discharged from ICU to the medical ward on day 22, mobilising well with improving respiratory function and respiratory reserve. He recovered well and returned to England eight weeks after admission.

DISCUSSION

Mycoplasmas are the smallest free-living microorganisms. There are in excess of 120 species of Mycoplasma, however only three are documented to cause disease in humans. MP is a common cause of atypical pneumonia in humans, accounting for 10 to 30% of all cases of pneumonia (1). It is associated with extrapulmonary disease, including the mucocutaneous condition Stevens Johnson syndrome and is the focus of this discussion 2-7.

There have been over 70 cases of Mycoplasma-associated Stevens Johnson syndrome reported in the literature'. The overall frequency of Stevens Johnson syndrome irrespective of cause has been quoted as 1.2 to 10.3 cases per million individuals per year in a population-based study of this syndrome with a mortality rate of about 5% (9). The Mycoplasma-associated syndrome appears to be more common in males, with a ratio of 2:1. Various infectious diseases have been described to cause Stevens Johnson syndrome (Table 1). Over 100 drugs have been implicated, the most common of these being antibiotics, non-sterodal anti-inflammatory drugs and anticonvulsants (10-14).

Clinical manifestations

Our patient initially presented with a prodromal illness characterised by upper respiratory tract symptoms. Indeed, in a case series by Levy et al (15), the most common symptoms included fever (81%), dry cough (78%), headache and malaise (43%), pharyngitis (43%), sore eyes (15%) and nasal discharge (15%). Levy et al suggest that prodromal symptoms usually occur two to 14 days prior to the development of cutaneous lesions.

The progression of cutaneous lesions seen in our case is typical of the course described in the literature. Skin involvement usually begins as macules, which are poorly defined, having purpuric centres, often with a vesiculobullous component. The lesions are symmetrical and are described as burning or painful, progressing over the following days. Different stages of eruptions may be present. Levy et al (15) reported the predominant component of the exanthema as an erythematous maculopapular type, with the predominant distribution being the upper limbs (59%), lower limbs (53%) and trunk (46%). The scalp seems rarely affected. Lesions may occur on any mucosal surface, representing one of the hallmarks of the syndrome. The oral mucosa is almost always involved, with the conjunctiva and genitalia being involved in 59-85% and 65% respectively (8).

Diagnosis

The diagnosis of the Mycoplasma associated syndrome remains primarily clinical. The leucocyte count on admission is often normal or slightly raised (15). Mycoplasma pneumoniae can be cultured from various specimens including sputum, nasopharyngeal aspirates and bronchial lavage washings. Fluid from skin lesions and blisters may culture the Mycoplasma, however the yield is low. Chest X-ray findings are non-specific, variable and often normal (15). The most widely used serological test to detect the Mycoplasma is the complement fixation test. A positive result is defined as a single titre greater than or equal to 1:32 or alternatively a fourfold or greater increase in titre in paired sera collected two to four weeks apart (16).

Management

The treatment of the infection and syndrome involves supportive management, antibiotic therapy and wound care of cutaneous lesions to prevent secondary infection. The management requires early recognition and cessation of any potential causes or precipitants known to cause Stevens Johnson syndrome. Treatment options include symptomatic supportive treatment alone, treatment with steroids, treatment with antibiotics, or a combination approach.

Mycoplasma pneumoniae may be treated with macrolides, doxycycline or flouroquinolones (17,18). Azithromycin seems to be the most active drug and is considered the antibiotic of first choice. Our patient was treated empirically for community-aquired pneumonia with meropenem, azithromycin, prednisolone, bronchodilators and oxygen. Therefore treatment seems reasonable, particularly after Mycoplasma pneumoniae was isolated as the causative organism.

In the literature, the use of corticosteroids for Stevens Johnson syndrome is a controversial and debated topic. The belief that steroids may be beneficial is due to the thought that the skin lesions and systemic effects of the syndrome may be an immune hypersensitivity response. Tripathi et al (19) analysed 67 patients with this syndrome who were treated with corticosteroids, all of whom went on to have favourable outcomes.

Steroids are known to have potential complications, including peptic ulceration, infection and prolonged admissions, and some studies have shown no improvement or in fact a detrimental effect in patients with this syndrome. Halebian et al (20) reported an increased mortality (66% vs. 33%) due to sepsis in patients receiving steroid treatment for Stevens Johnson syndrome of unknown aetiology.

CONCLUSION

Although the Mycoplasma associated syndrome is rare, it is important for the clinician to be aware of this condition as it has a significant morbidity and mortality. Management is essentially supportive in nature, combined with targeted antibiotic therapy. Further specific therapy is under investigation, with steroids and immunoglobulin showing a potentially beneficial role.

Accepted for publication on January 5, 2007.

REFERENCES

(1.) Cherry JD, Ching N. Mycoplasma and ureaplasma infections. In: Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. 5th ed. Pennsylvania. W B. Saunders 2004; 2516-2547.

(2.) Lind K. Mucocutaneous reactions during Mycoplasma pneumoniae infection. Lancet 1978; 1:655.

(3.) Meseguer MA, de Rafael L, Vidal ML. Stevens Johnson syndrome with isolation of Mycoplasma pneumoniae from skin lesions. Eur J Clin Microbiol 1986; 5:167-168.

(4.) Stutman HR. Stevens Johnson syndrome and Mycoplasma pneumoniae: evidence for cutaneous infection. J Pediatr 1987; 111:845-847.

(5.) Ludlam GB, Bridges JB. Association of Stevens Johnson syndrome with antibody for Mycoplasma pneumoniae. Lancet 1964; 41:958-959.

(6.) Katz HI, Wooten JW, Davis RG, Griffin JP Stevens Johnson syndrome. Report of a case associated with culturally proven Mycoplasma pneumoniae infection. JAMA 1967; 199:504-506.

(7.) Cannell H, Churcher GM, Milton Thompson GJ. Stevens Johnson syndrome associated with Mycoplasma pneumoniae infection. Br J Dermatol 1969; 81:196-199.

(8.) Tay YK, Huff JC, Weston WL. Mycoplasma pneumoniae infection is associated with Stevens-Johnson syndrome, not erythema multiforme (von Hebra). J Am Acad Dermatol 1996; 35:757-760.

(9.) Strom BL, Carson JL, Halpern AC, Schinnar R, Snyder ES, Shaw M et al. A population-based study of Stevens-Johnson syndrome. Incidence and antecedent drug exposures. Arch Dermatol 1991; 127:831-838.

(10.) Lam NS, Yang YH, Wang LC, Lin YT, Chiang BL. Clinical characteristics of childhood erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis in Taiwanese children. J Microbiol Immunol Infect 2004; 37:366-370.

(11.) Dietrich A, Kawakubo Y, Rzany B, Mockenhaupt M, Simon JC, Schopf E. Low N-acetylating capacity in patients with Stevens Johnson syndrome and toxic epidermal necrolysis. Exp Dermatol 1995; 4:313-316.

(12.) Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T et al. Medication use and the risk of Stevens Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 1995; 333:1600-1607.

(13.) Leaute-Labreze C, Lamireau T, Chawki D, Maleville J, Taieb A. Diagnosis, classification, and management of erythema multiforme and Stevens Johnson syndrome. Arch Dis Child 2000; 83:347-352.

(14.) Huang RY, Liu HN, Wong CK. [Stevens Johnson syndrome: a review of 42 cases]. Zhonghua Yi Xue Za Zhi (Taipei) 1993; 51:225-230.

(15.) Levy M, Shear NH. Mycoplasma pneumoniae infections and Stevens Johnson syndrome. Report of eight cases and review of the literature. Clin Pediatr (Phila) 1991; 30:42-49.

(16.) Jacobs E. Serological diagnosis of Mycoplasma pneumoniae infections: a critical review of current procedures. Clin Infect Dis 1993; 17 Suppl 1:S79-82.

(17.) Critchley IA, Jones ME, Heinze PD, Hubbard D, Engler HD, Evangelista AT et al. In vitro activity of levofloxacin against contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North America and Europe. Clin Microbiol Infect 2002; 8:214-221.

(18.) Cunha BA. The antibiotic treatment of community-acquired, atypical, and nosocomial pneumonias. Med Clin North Am 1995; 79:581-597.

(19.) Tripathi A, Ditto AM, Grammer LC, Greenberger PA, McGrath KG, Zeiss CR et al. Corticosteroid therapy in an additional 13 cases of Stevens Johnson syndrome: a total series of 67 cases. Allergy Asthma Proc 2000; 21:101-105.

(20.) Halebian PH, Corder VJ, Madden MR, Finklestein JL, Shires GT. Improved burn center survival of patients with toxic epidermal necrolysis managed without corticosteroids. Ann Surg 1986; 204:503-512.

J. M. MULVEY *, A. PADOWITZ([dagger]), M. LINDLEY-JONES([double dagger]), R. NICKELS[section]

Departments of Intensive Care and Medicine, The Tweed Hospital, Tweed Heads, New South Wales, Australia

* M.B., B.S.(Hons), B.Sc. (Hons), Anaesthetics Trainee, Department of Intensive Care.

([dagger]) M.B.B.cH., Emergency Trainee, Department of Intensive Care.

([double dagger]) M.A., M.B., B.S., FR.C.S., F.J.F.I.C.M., Consultant, Department of Intensive Care.

[section] M.B.Ch.B., M.R.C.P.(Lond), F.R.A.C.P, Respiratory Physician, Department of Medicine.

Address for reprints: Dr J. Mulvey, Department of Intensive Care, The Tweed Hospital, Tweed Heads, N.S.W 2485.
TABLE 1
Infectious diseases associated with Stevens Johnson syndrome

Viral infections Bacterial infections Fungal/parasitic

Adenovirus Legionella Syphilis

Ebstein Barr Virus Mycoplasma Deep fungal
 infections

Enteroviruses Pseudomonas

Herpes Simplex Tuberculosis

Influenza Streptococci

Measles Yersinia

Mumps

Varicella
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Article Details
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Author:Mulvey, J.M.; Padowitz, A.; Lindley-Jones, M.; Nickels, R.
Publication:Anaesthesia and Intensive Care
Article Type:Clinical report
Geographic Code:8AUST
Date:Jun 1, 2007
Words:2417
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