Long-Nian Li,Hui-Fang Yang,Yun Lai,Cong You,Zhao-Lin Zeng,De-Dong Liu,Xiao-Ying Ye,?

1Department of Dermatology,2Laboratory Medicine Division,First Affiliated Hospital of Gannan Medical University,Ganzhou,Jiangxi 341000,China.

Introduction

Purpura fulminans(PF)was first described in 18861and is characterized as a rare syndrome with a rapidly progressive course of hemorrhagic infarction of the skin and soft tissue necrosis.It mainly occurs in children and rarely in adults.1PF is a life-threatening disease that can be a clinical presentation of toxic shock syndrome(TSS).2The most common infectious etiology is cocci,and routine use of antibiotics for this disease is well recognized.However,another etiology,influenza virus,is often neglected.We herein report a case involving an older patient with TSS presenting with PF,in which Streptococcus pyogenes(S.pyogenes)accompanied by influenza virus might have played an important role,in order to arise the attention of clinician to the infection of the influenza virus in the pathogenesis of TSS.

Case report

A 76-year-old man with eczema developed swelling of the right knee for one hour.He had no history of trauma,but he reported having had a cold with antibody(IgM)to influenza A virus(IAV).Although the patient had a fever(39.0°C),blood and biochemical examinations showed no obvious abnormality. Physical examination showed swelling of the right thigh,which was covered by erythema(Fig.1A).A percutaneous puncture produced dark red fluid.Smear cytology of the fluid revealed Gram-positive cocci, and empirical vancomycin hydrochloride and cefoperazone sodium/sulbactam sodium were therefore administered. However, the skin lesions continued to develop,and the color of the skin turned to purple-black(Fig.1B).

Magnetic resonance imaging showed diffuse edema of the subcutaneous and intermuscular tissues (Fig. 2).During the next 32hours,the patient developed diffuse cyanotic skin lesions (Fig. 1C and D), respiratory insufficiency,and hypotension despite intensive care unit management.Unfortunately,the patient died of multiple organ failure(MOF).One day after his death,the blood and puncture fluid cultures showed growth of S.pyogenes(Fig.1E),which was resistant to vancomycin.

PF was initially considered in our patient because of his fever,hypotension,and hemorrhagic skin lesions.However,MOF and shock occurred during the clinical course.Based on these manifestations,TSS presenting with PF was finally considered.

Discussion

PF is a dermatologic manifestation of an underlying lifethreatening condition associated with disseminated intravascular coagulation and skin necrosis.Three forms of PF have been described to date:neonatal,chronic,and acute infectious PF.1The last two forms are related to viral infection, especially IAV, which could have a profound effect on susceptibility to superinfections.In patients with acute infectious PF,superinfections associated with IAV can be caused by S.pyogenes,3also known as group A beta-hemolytic streptococcus(GAS),which can be carried asymptomatically on human skin.GAS infections are related to the patient’s health status and breaches of his or her external defense system,even breaches caused by minor injuries such as scratches,which occurred in our patient was eczema. The mechanism of infection may involve either contiguous spread from an existing infection or direct inoculation.GAS then quickly adapts to the host’s environment through several molecular functions,4such as altering the transcriptome in response to growth conditions and producing proteins designed to subvert the body’s immune system.Notably,IAV infection can influence the severity of superinfections by increasing production of the protein tenascin C,which can potentiate tissue damage by increasing the synthesis of proinflammatory cytokines.5Additionally, the pathogenesis may be contingent on the molecular genetics of the host.6The spread of infection finally causes vascular occlusion,ischemia,and necrosis.Acidosis,electrolyte abnormalities,and coagulopathy subsequently develop.Septicemia and MOF ensue with systemic toxicity.

The initial clinical similarity of TSS to cellulitis and PF makes early diagnosis of TSS difficult.Because of the rapid clinical progression,dermatologists should be aware of this disease and immediately initiate aggressive treatment for suspected cases,especially treatment against IAV.Progression to death requires contributions from the virus,bacteria,and host. Further, research is needed because of the undefined interactions between the host and pathogens.

Acknowledgement

We thank the patient’s family for providing the patient’s information.

Figure 1.Clinical presentation of the patient.Skin lesions at onset(A),5h later(B),and 15hours later(C and D).(E)Puncture fluid culture showing growth of Streptococcus pyogenes.

Figure 2.Magnetic resonance imaging showing obvious swelling of the skin,subcutaneous fat,and partial muscle tissues of the right thigh 5h after the onset of symptoms.(A)The coronal MRI image.(B)The axial MRI image.