Scleroderma digital ulcers complicated by infection with fecal pathogens
Digital ulcers represent one of the most frequent complications of systemic sclerosis (SSc; scleroderma); they are very painful, scarcely responsive to treatment, and often responsible for marked limitations on daily activities, including patient self-care. Infectious complications may severely compromise the outcome of skin lesions in a significant percentage of patients. Numerous pathogens of different origin may be involved, including bacteria from patient endogenous flora. Here we evaluated the possible involvement of fecal pathogens in scleroderma digital ulcers.
Among a series of 82 SSc patients with digital ulcers, we retrospectively analyzed 42 subjects with clinical signs of local bacterial infection. All digital ulcers with suspected infection have been investigated by microbiologic examinations.
Bacterial infection was confirmed in all 42 patients investigated; in particular, Staphylococcus aureus were the most frequently found (50%). Interestingly, 11 (26%) of 42 patients showed digital ulcers infected with intestinal bacteria; specifically, 7 patients were positive for Escherichia coli and 4 for Enterococcus faecalis. Diffuse cutaneous SSc patients were more numerous in this subgroup versus the other 31 patients (Fisher's P = 0.011).
A number of effective measures involving health care personnel and hospital environment are essential in the management of digital ulcers and prevention of infectious complications. In addition, the prevalence of fecal pathogens in one-quarter of cases, never reported previously, suggests an important role of a patient's self-care limitations, mainly during intercurrent home medications. Consequently, methodical education on hand hygiene of both patients and relatives, frequently involved in ulcer medications, is mandatory to avoid such deleterious complications.
Systemic sclerosis (SSc; scleroderma) is a connective tissue disease characterized by a variable degree of fibrosis of skin and internal organs, widespread microangiopathy, and immune system disorder (1, 2).
Symptoms related to vascular disorder appear very early in the course of the disease and typical digital ulcers represent one of the most frequent and burdensome clinical manifestations of SSc. More than 50% of scleroderma patients experience digital ulcers; these typical skin lesions are often nonhealing and recurrent, and may involve many fingers at the same time. Digital ulcers severely limit scleroderma patients in everyday personal and professional tasks. Patients frequently require hospitalization because of clinical complications such as gangrene, infection of soft tissue, and/or osteomyelitis, leading to need for amputation (3–6).
The presence of pain and bandages, frequently used to maintain the correct moisture and to promote the efficacy of contact medications, very often may limit personal hygiene with an increased risk of local infection and difficult ulcer healing.
The present study retrospectively analyzed microbiologic findings from scleroderma digital ulcers and suspected bacterial infection.
Significance & Innovations
Digital ulcers represent one of the most frequent and burdensome clinical manifestations of scleroderma, are often nonhealing or recurrent, and are responsible for a severe limitation of patients' everyday tasks.
A high incidence of fecal pathogens in infected scleroderma digital ulcers was found, underlining the importance of hand hygiene of patients and relatives, along with health care operators.
Patients and methods
During the last 3 years, we observed at our Rheumatology Unit 82 SSc patients with complicating digital ulcers. In 42 (51.2%) of 82 subjects with clear signs of possible bacterial infection, microbiologic examinations were performed; specifically, cutaneous swabs were evaluated in the presence of perilesional erythema or swelling, abundant and/or purulent exudates, and odor (7). All swabs were performed at the level of necrotic areas, and dried exudates, slough, and/or dressing residue was removed with sterile saline solution and surgical debridement. Then a sterile swab with a cotton tip was used to better recover infectious agents from the site. The tip was moistened with lactate ringer if the wound was too dry. Taking care that the swab remained in contact with only the wound surface, it was moved in a zigzag course while being rotated between the fingers (8). The material from both the wound bed and margins was collected; finally, the swabs were quickly replaced in the container and transferred to the laboratory.
The presence of an infectious microorganism was identified by means of agglutination tests with antibodies specific for bacterial surface antigens, using protein or DNA sequencing.
Table 1 shows the main clinicoserologic and microbiologic features of the 42 SSc patients with digital ulcer infection. No patients underwent immunosuppressant therapy. Moreover, no patients activated the home nursing service, providing the ulcer care by themselves or with the help of relatives.
Table 1. Data of 42 systemic sclerosis patients with infected digital ulcers
|Clinicoserologic data|| |
| Male/female, no.||5/37|
| Age, mean ± SD years||56.3 ± 15.8|
| Disease duration, mean ± SD years||11.1 ± 7.9|
| Skin subsets, no.|| |
| Limited cutaneous||31|
| Diffuse cutaneous||11|
| Serology, no.|| |
| Smokers/nonsmokers, no.||4/38|
|Microbiologic data, no. (%)|| |
| Infections|| |
| Escherichia coli, Enterococcus faecalis||11 (26)|
| Pseudomonas aeruginosa||5 (12)|
| Staphylococcus aureus||21 (50)|
| Others*||5 (12)|
During the 3 years of the retrospective study, all 42 SSc patients showed at least 1 infected lesion. Interestingly, 11 of 42 patients evaluated showed skin lesions infected with typical pathogens from intestinal origin; in particular, 7 patients were positive for Escherichia coli and 4 for Enterococcus faecalis. More habitual infectious agents were detected in the remaining 31 of 42 patients; in particular, Staphylococcus aureus was detected in 21 (50%) of 42 and Pseudomonas aeruginosa was detected in 5 (12%) of 42, while other less frequent pathogens were found in the remaining 5 (12%) of 42 individuals. All of the observed infections were responsive to common antibiotic therapy. Ulcers infected with fecal pathogens were more sensitive to antibiotics than those infected with P aeruginosa. While a faster resolution of infection was generally observed with fecal pathogens, reinfection was more frequently observed in these patients.
Statistical analysis between SSc patients with ulcers infected with intestinal bacteria versus the others evidenced a significantly increased percentage of diffuse cutaneous SSc among the first ones (6 of 11 versus 5 of 31 SSc patients; Fisher's P = 0.011). No other correlations were found in regard to age, sex, disease duration, and serology, or in regard to the clinical features of ulcers, i.e., size, duration, and stage of healing.
The present study first focused on the significant proportion of fecal pathogens in infected scleroderma digital ulcers. The main pathogenetic mechanisms of infectious complications may be correlated with scleroderma microangiopathy and defective immune system activity, with the possible contribution of immunosuppressive treatments. Altogether these factors represent the most favorable substrate for ulcer infection. Scleroderma digital ulcers per se are characterized by a low tendency to heal; furthermore, infectious complications are particularly detrimental and often responsible for adverse prognosis up to gangrene and amputation. During the wound care procedures the patients can be exposed to a variety of exogenous microorganisms; the most common sources of infectious agents are the patient him/herself, other patients, health care personnel, and the hospital environment, mainly contaminated medical equipments and/or medications (9). Although digital ulcers occur very frequently in the course of the disease, at the moment validated management guidelines are not available. Our experience suggests that a global approach, including both local and systemic treatment, is always required. In particular, vasoactive drugs represent the first-line systemic treatment, particularly prostanoid infusions.
Oral treatment with bosentan is usefully employed to prevent the appearance of new lesions in scleroderma patients with a history of digital ulcers (10) by improving endothelial function (11). Other authors suggested the efficacy of sildenafil (12, 13) or tadalafil (14), alone or in combination with bosentan (15), on the healing of digital ulcers, even if further studies are required to confirm these data.
Moreover, local treatment is fundamental; it is based on wound bed preparation, according to the “TIME” (Tissue management; Inflammation and Infection control; Moisture balance; Epithelial [Edge] advancement) approach (16). Since digital ulcers are extremely painful, particularly at night with a deep impact on sleep and quality of life, appropriate analgesic therapy is often necessary, according to the World Health Organization recommendations for chronic pain; the use of opioids should be preferred to nonsteroidal antiinflammatory drugs.
Overall, we closely followed scleroderma patients with severe cutaneous ulcers in a dedicated wound care clinic, in which an expert team of rheumatologists and nurses was involved. The prevention and treatment of preexisting local or systemic infections is a crucial step in wound bed preparation; during all therapeutic procedures rigorous asepsis is mandatory. It must include hand hygiene of health care workers, careful surveillance of the hospital environment, and cross-transmission of infection among patients (17). Another important reservoir is patients' endogenous flora; specifically, bacteria residing on the skin, mucous membranes, and gastrointestinal tract. Besides the most common agents such as P aeruginosa and S aureus, the presence of fecal pathogens strongly emphasizes the role of intercurrent home medications. The patient's self-care, especially hand hygiene, is often inadequate because of skin and joint involvement and is often responsible for flexion contractures of the fingers and upper extremities; the presence of digital ulcers further compromises hand hygiene after defecation. These SSc features are generally more frequent in patients belonging to the diffuse skin subset; consistently, we found a significantly increased percentage of diffuse SSc patients among those with ulcers infected with fecal bacteria.
Epidemiologic studies underlined the positive effects of simple hand washing for preventing transmissions of pathogens (18). The use of antiseptic hand soaps, mainly those containing chlorhexidine, and alcohol-based hand rubs are usefully utilized; unfortunately, SSc patients with digital ulcers cannot use these antiseptic remedies, which can enhance local pain and impair the granulation tissue of skin lesions. Methodical education on hand hygiene of both patients and relatives, frequently involved in ulcer medications, is mandatory to avoid such harmful complications. Home medications of digital ulcers by patients themselves or with the help of relatives should be carried out using disposable gloves, even if some patients with painful ulcers of the fingertips may have serious difficulties in adopting this simple but important measure. Health care workers must carefully recommend that scleroderma patients perform accurate hand hygiene immediately before wearing gloves to touch chronic wounds, and also when ulcers are localized on fingers.
Finally, we underline the surprisingly high incidence of fecal pathogens in infected scleroderma digital ulcers; this peculiar complication evidenced in one-quarter of cases has never been reported previously. Therefore, a global management strategy is necessary; besides health care operators, both patients and relatives should be involved in the prevention and treatment of such deleterious complications.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Giuggioli had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Giuggioli, Ferri.
Acquisition of data. Giuggioli, Manfredi, Colaci, Lumetti.
Analysis and interpretation of data. Manfredi, Colaci, Ferri.