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Keywords:

  • anti-Chlamydiae antibody;
  • Chlamydia pneumonia;
  • erythema exsudativum multiforme;
  • silent infection of Chlamydia pneumonia

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Reports
  5. Discussion
  6. Acknowledgment
  7. References

We report two cases of erythema exsudativum multiforme (EEM) that we concluded were caused by infections with Chlamydia pneumoniae. High titers of IgG antibody for Chlamydia pneumoniae were shown in the sera of both cases. One case showed the classical symptoms of pneumonia together with radiological changes in the chest; the other case did not show these symptoms. To the best of our knowledge, only three cases of erythema multiforme associated with Chlamydia pneumoniae infection have been reported.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Reports
  5. Discussion
  6. Acknowledgment
  7. References

Erythema exsudativum multiforme (EEM) refers to an array of heterogeneous clinical illnesses characterized by symmetrical target or iris lesions.

Many potential causes of EEM have been reported previously, such as viral or bacterial infections, medication adverse effects, radiation exposure and collagen disease. Although infections by Herpes simplex virus and Mycoplasma pneumoniae are well-known causes of EEM,1 infection by Chlamydia pneumoniae has very rarely been reported. In this report, we describe two cases in which C. pneumoniae infection was shown to be the probable cause.

Case Reports

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Reports
  5. Discussion
  6. Acknowledgment
  7. References

Case 1

A 44-year-old Japanese man presented at our hospital with a 4-day history of high fever, dry cough and eruptions over the whole body. He had no past history of illness or skin eruptions caused by drugs. At the time of the initial examination, multiple, partly coalesced, thumb-sized erythemas were distributed on the trunk and limbs (Fig. 1a). In addition, blister formations were seen especially on both distal forearms (Fig. 1b). There was no conjunctival injection or enanthema. In addition to the skin condition, the patient had a high fever of 39°C and a non-productive cough. At this point, EEM was suspected clinically. In order to confirm the clinical diagnosis of EEM, we performed a biopsy from an area of erythematous skin that carried blisters.

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Figure 1.  Clinical manifestations of case 1 at his first visit. (a) Multiple erythemas were scattered over the whole body. (b) Blister formations were seen on both distal forearms.

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The results of blood tests were: white blood cells, 13 100/μL; C-reactive protein (CRP), 3.3 mg/dL; alanine aminotransferase, 73 IU/L; γ-glutamyl transpeptidase, 221 IU/L; anti-C. pneumoniae immunoglobulin (Ig)G antibody titer, 2.218 (normal, <1.10); IgA antibody titer, 2.655 (normal, <1.10); IgM antibody titer, 3.001 (normal, <1.10); Mycoplasma antibody, negative; anti-streptolysin O (ASLO), 75 IU/mL; rheumatoid factor, less than 20 IU/mL; antinuclear antibody, negative; anti-double-stranded deoxyribonucleic acid antibody (ANA), negative; anti-Sjögren syndrome A antibody, negative; anti-Sjögren syndrome B antibody, negative; chest X-ray showed a slight permeability decay of both lower lung fields (Fig. 2a); and chest computed tomography (CT) showed multiple ground-glass appearances with bronchus extensions accompanied by traction in both lung fields, slightly swollen lymph nodes scattered around the bronchi, and a small quantity of pleural effusion, without honeycomb lung, which was diagnosed as non-specific interstitial pneumonia (Fig. 2b). Histopathology of the skin biopsy showed acanthosis with epidermal necrosis and many subepidermal blister formations. There was edema in the upper layer of the dermis with lymphocyte infiltration around the dilated blood vessels (Fig. 3).

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Figure 2.  (a) Chest X-ray shows permeability decay in both lower lung fields. (b) Chest computed tomography shows non-specific interstitial pneumonia.

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image

Figure 3.  Biopsy of a skin lesion. Many subepidermal blisters were observed as well as lymphocyte infiltrates around the dilated blood vessels (hematoxylin–eosin, original magnification ×40).

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The patient was treated with p.o. administration of an anti-allergy drug and topical application of steroid and i.v. antibiotic administration (cefazolin sodium) because the blood test suggested a bacterial infection. In addition, due to the chest CT indicating non-specific interstitial pneumonia, we added clarithromycin. A week later, his fever had decreased, the non-productive cough had improved and the erythema had changed into pigmentation.

Case 2

A 65-year-old Japanese man was admitted to our hospital with a few days’ history of fever and erythema on the whole body, and he also complained of arthritic pain and general malaise. The patient had no past history of illness or of medication adverse effects before eruptions appeared. At the time of the initial consultation, multiple erythemas were scattered on the trunk and limbs. Some of the erythemas had coalesced (Fig. 4). There was no conjunctival injection or enanthema. In addition to the skin condition, the patient had a high fever of 39°C. We diagnosed the case as EEM based on clinical findings.

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Figure 4.  Multiple erythemas of case 2 at his first visit.

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The results of blood tests were as follows: white blood cells, 5 900 /μL; CRP, 11.0 mg/dL; anti-C. pneumoniae IgG antibody titer, 0.818 (normal, <1.10); IgA antibody titer, 1.916 (normal, <1.10); IgM antibody titer, 2.810 (normal, <1.10); Mycoplasma antibody, negative; ASLO, 73 IU/mL; herpes simplex IgG, negative; herpes simplex IgM, negative; chest X-ray showed no remarkable change; and anti-C. pneumoniae IgG antibody titer in serum 2 weeks after the first test, higher than 1.35. After treatment with an oral anti-allergy drug and an antibiotic (minocycline hydrochloride) for 1 week, the eruption had improved.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Reports
  5. Discussion
  6. Acknowledgment
  7. References

Erythema exsudativum multiforme is a disease concept that was proposed by Ferdinand von Hebra in 1866.2 Although the precise mechanism of the disease is still unknown, viral or bacterial infections, medication adverse effects, radiation exposure and whole body diseases such as collagen disease may trigger EEM. Among them, herpes simplex virus is the most commonly identified cause of the infectious disease, and M. pneumoniae has also been reported frequently.1 In case 1, the titers of anti-C. pneumoniae IgG, IgA and IgM antibodies were positive serologically, and the interstitial pneumonia caused by C. pneumoniae was confirmed by the chest X-ray and the CT. Furthermore, we excluded streptococcal infection as the cause of EEM because the value of ASLO was within the limits of normal and collagen disease was ruled out because ANA were negative. Then, various bacterial cultures using pharyngeal and sputum culture were all negative. Aerobic bacterial culture revealed no remarkable findings and there had been no history of contrast medium and medication before eruptions appeared. Therefore, we concluded that infection by C. pneumoniae was the cause of EEM by excluding other causes described before. In case 2, the initial blood test showed no abnormal findings such as high concentration of CRP or high titers of anti-C. pneumoniae IgA and IgM antibodies. Although there were symptoms of a cold (such as high fever), general malaise, arthritic pain, or a non-productive cough were not apparent, and a chest X-ray showed no specific change. Because there had been no past history of illness or of any particular medication adverse affects before eruptions appeared, the value of ASLO was normal, an increased titer of anti-C. pneumoniae IgG antibody after 2 weeks indicated that the cause of the initial infection also in this case was C. pneumoniae.

Among four kinds of Chlamydia species, three kinds (Chlamydia trachomatis, Chlamydia psittaci and C. pneumoniae) have been reported to be pathogenic in humans. When infected with C. pneumoniae, high fever, non-productive cough and abnormalities in chest X-ray are seen in many cases, but silent infections without such findings are also known.3

Although C. psittaci has been known to cause EEM, C. pneumoniae has been reported as the cause of EEM in only three cases.4,5 In our opinion, the C. pneumoniae infection plays a very important role in attributing to EEM in our two cases; of course, we cannot deny the other causes of EEM.

In most institutions, the titers of anti-C. pneumoniae IgG, IgA and IgM antibodies are not examined routinely. However, at least in cases of EEM associated with pneumonia, it is worth examining these titers. Moreover, there should be some cases of silent infection in which the titer of antibody for C. pneumoniae in the paired serum samples shows positivity, as in our case 2; such cases need to be carefully evaluated. In order to diagnose EEM, we think that it is important to examine the titers of anti-C. pneumoniae IgG, IgA and IgM antibody routinely, if possible, and to exclude other causes of EEM such as streptococcal infection, collagen disease and adverse effect of contrast medium and medication.

Acknowledgment

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Reports
  5. Discussion
  6. Acknowledgment
  7. References

The authors are grateful to Emeritus Professor Dr Akira Ishibashi (Department of Dermatology, National Defense Medical College) for his important suggestions.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case Reports
  5. Discussion
  6. Acknowledgment
  7. References
  • 1
    Vedrana B, Liborija L, Mirna S. Prominent features and variations in clinical presentation of erythema multiforme. Acta Clin Croat 2007; 46: 5562.
  • 2
    William DJ, Timothy GB, Dirk ME. Erythema multiforme. In: Andrew’s disease of the skin clinical dermatology, 10th edn. Philadelphia: Saunders, 2006; 140142.
  • 3
    Naoyuki M, Yoshihito N, Masamitsu N, Hiroshi F, Toshiharu M. Prevalence of asymptomatic infection with chlamydia pneumoniae in subjectively healthy adults. Chest 2001; 119: 14161419.
  • 4
    Terada K, Hiraga Y, Mori R et al. Double infection of Chlamydia pneumoniae and Mycoplasma pneumoniae in children. Kansenshogaku Zassh 1996; 70: 11761180, (in Japanese with English abstract).
  • 5
    Sadda D, Velasco S, Vabres P, Guillet G. Erythema multiforme majus and Chlamydia pneumoniae infection. Ann Dermatol Venereol 2006; 133: 10011004, (in French with English abstract).