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Cellulitis following pelvic lymph node dissection

Cellulitis following pelvic lymph node dissection
Literature review current through: Jan 2024.
This topic last updated: May 23, 2023.

INTRODUCTION — Acute cellulitis following pelvic lymph node dissection is a rarely reported syndrome that occurs in women who have undergone pelvic surgery for gynecologic carcinoma that included local lymph node dissection, specifically cervical, uterine, or vulvar carcinoma.

This topic will address the epidemiology, microbiology, clinical manifestations, and treatment of cellulitis following pelvic lymph node dissection. An in-depth description of the diagnosis and management of cellulitis and erysipelas not associated with pelvic lymph node dissection is found elsewhere. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis" and "Acute cellulitis and erysipelas in adults: Treatment".)

EPIDEMIOLOGY — Reported cases of cellulitis following pelvic lymph node dissection have all occurred in women who have undergone local lymph node dissection for gynecologic cancer, specifically cervical, uterine, or vulvar cancer [1-7]. Two reports from the Netherlands in the late 1980s provide the most clinical information characterizing these syndromes [1,2]. Subsequent case reports from the United States confirmed these initial observations [3-5].

The incidence of cellulitis following pelvic lymph node dissection is uncertain. In a series of 270 women who had undergone pelvic lymphadenectomy with radical hysterectomy, cellulitis eventually occurred in 4 percent; collectively, nine women experienced 17 episodes of cellulitis during over 14,000 patient months of follow-up [1]. In a subsequent study of 126 women who had undergone radical vulvectomy with superficial and deep inguinal lymphadenectomy for vulvar carcinoma, subsequent cellulitis occurred in 26 percent of patients [2].

Among patients with pelvic lymph node dissection, identified risk factors associated with the development of cellulitis include post-operative pelvic irradiation and vaginal or cervical colonization with beta-hemolytic streptococci prior to surgery.

MICROBIOLOGY — For most patients with cellulitis after surgery for gynecologic cancer, specific pathogens are not identified.

In cases in which pathogens have been recovered, most of the isolates were non-group A, beta-hemolytic streptococci, specifically Streptococcus agalactiae (ie, Group B Streptococcus) or Streptococcus mitis/oralis (ie, viridans streptococci) [1-5,7]. These organisms have been recovered from both blood and vaginal cultures of affected patients and appear to have a proclivity to produce soft tissue infections in the setting of venous and/or lymphatic compromise. Of note, S. mitis/oralis and other species of viridans group streptococci only rarely cause classic cellulitis not associated with pelvic node dissection. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Although non-group A, beta-hemolytic streptococci cause the majority of cases, other organisms, such as Staphylococcus aureus and Streptococcus pyogenes (group A Streptococcus), may play a role as they do in cases of classic cellulitis.

CLINICAL MANIFESTATIONS

General symptoms — Cellulitis following pelvic lymph node dissection presents similarly to classic cellulitis, with skin erythema, edema, and tenderness. Fever, chills, and systemic toxicity are often present. Septic shock is unusual and should prompt consideration of other conditions, such as toxic shock syndrome or necrotizing fasciitis, as discussed elsewhere. (See 'Differential diagnosis' below.)

The erythema typically occurs over the lower abdominal wall, inguinal area, and/or the proximal thigh. In some patients, the erythema may have an atypical macular appearance or occur in patches, as opposed to the confluent erythema of classic cellulitis. Some patients have findings more consistent with erysipelas (ie, raised erythema with a clearly demarcated border).

Recurrent episodes may occur and are typically similar to previous bouts in terms of symptoms, location, and severity of illness. They usually occur without antecedent precipitating events, although vaginal intercourse appears to initiate infection in some patients, as described below [5]. (See 'Timing of onset' below.)

Timing of onset — The average time to the first episode of cellulitis following pelvic lymph node dissection is 29 months (range 4 to 52 months) [1,2].

In some individuals, the cellulitic episode occurs following vaginal intercourse and is termed "streptococcal sex syndrome" [5,6]. In such individuals, cellulitis may recur after subsequent episodes of vaginal intercourse.

DIAGNOSIS AND EVALUATION — The diagnosis of cellulitis following pelvic lymph node dissection is based on clinical signs and symptoms. The infection should be suspected in women with a history of pelvic lymph node dissection who present with skin erythema, edema, and tenderness in the lower abdominal wall, inguinal area, and/or the proximal thigh, especially if such findings occur after vaginal intercourse.

Like other forms of cellulitis, no diagnostic studies confirm or rule out the diagnosis. For patients who have systemic findings, we suggest obtaining blood cultures (two sets from separate sites). For patients whose cellulitis follows vaginal intercourse, vaginal cultures may help to guide therapeutic and prophylactic antimicrobial selection.

DIFFERENTIAL DIAGNOSIS

Necrotizing fasciitis – This syndrome is characterized by deeper soft tissue infection involving the muscle fascia and manifests with pain out of proportion to examination findings and rapid progression. The diagnosis is confirmed with surgical exploration of the fascia. (See "Necrotizing soft tissue infections".)

Toxic shock syndrome – This syndrome can present with typical finding of cellulitis, but patients are hypotensive and have evidence of multiorgan failure (eg, acute kidney injury, elevated aminotransferases). (See "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis".)

Panniculitis – This uncommon syndrome is characterized by tissue inflammation of the subcutaneous fat and may have infectious or noninfectious causes. Patients typically have pain and tenderness deep to palpation with overlying chronic skin sclerosis; the diagnosis is confirmed with biopsy. (See "Panniculitis: Recognition and diagnosis".)

Inguinal lymphadenitis – Inflamed inguinal lymph nodes are tender and palpable and often have overlying skin erythema. The differential is broad and includes certain sexually transmitted infections. (See "Evaluation of peripheral lymphadenopathy in adults", section on 'Inguinal'.)

Intra-abdominal process (eg, appendicitis, ovarian cyst) – Lower quadrant abdominal pain and tenderness is the main feature of many abdominal pathologies; overlying skin erythema or induration is rare but can occur. Physical examination and radiographic imaging can typically diagnose these processes. (See "Acute appendicitis in adults: Clinical manifestations and differential diagnosis" and "Evaluation and management of ruptured ovarian cyst", section on 'Clinical findings'.)

TREATMENT

Empiric antibiotic selection — Antibiotic therapy is usually empiric, as pathogens are not often identified. However, if an organism is identified via blood culture, antibiotic therapy should be targeted to the causative organism.

Empiric coverage should include activity against beta-hemolytic streptococci; we also believe that S. aureus coverage is indicated given its relative frequency as a cause of classic cellulitis. This approach is consistent with the antibiotic selection for cellulitis in general. (See 'Microbiology' above and "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Microbiology'.)

Oral therapy is acceptable in many cases of cellulitis associated with pelvic lymph node dissection. More severe or complicated cases warrant parenteral therapy, specifically in those who have systemic toxicity (eg, fever >100.5°F/38°C, tachycardia), rapidly progressive or extensive erythema, or an immunocompromising condition. Further details regarding indications for parenteral therapy for cellulitis are found elsewhere. (See "Acute cellulitis and erysipelas in adults: Treatment", section on 'Indications for parenteral therapy'.)

Example regimens are listed below and generally match those suggested for patients with classic cellulitis (see "Acute cellulitis and erysipelas in adults: Treatment", section on 'Selecting an antibiotic regimen'):

Oral regimensDicloxacillin (500 mg every six hours), cephalexin (500 mg every six hours), or cefadroxil (500 mg every 12 hours or 1 g once daily).

For patients with purulent discharge or abscess, we suggest using a different regimen that includes methicillin-resistant S. aureus (MRSA) coverage. An example is trimethoprim-sulfamethoxazole (TMP-SMX; one to two double-strength tablets twice daily). (See "Acute cellulitis and erysipelas in adults: Treatment", section on 'Indications for MRSA coverage' and "Skin abscesses in adults: Treatment", section on 'Preferred regimens'.)

Parenteral regimens – Parenteral regimens include cefazolin (1 to 2 g every eight hours) or nafcillin (1 to 2 g every four hours). If MRSA coverage is warranted, then intravenous vancomycin can be used. Dosing of vancomycin is discussed in the table (table 1).

For patients who have severe sepsis or are immunocompromised, we generally broaden antibiotics to include coverage for aerobic gram-negative bacilli, including Pseudomonas aeruginosa, as discussed elsewhere. (See "Acute cellulitis and erysipelas in adults: Treatment", section on 'Patients with severe sepsis'.)

If an organism is identified via culture (eg, blood culture), the antibiotic regimen should be tailored to target the organism.

Duration of therapy — The optimal duration of therapy is uncertain and should extend for at least the typical duration for classic cellulitis (ie, five to six days). In general, antimicrobial therapy should be continued until clinical signs of infection have resolved. Response to therapy may be slow; most patients report improvement in pain before there is a noticeable decrease in erythema and swelling.

PREVENTION — For patients with recurrent cellulitis, we suggest antibiotic prophylaxis. The approach depends on whether sex is a precipitating factor:

For patients with recurrent cellulitis unrelated to sexual activity, we suggest continuous antibiotic suppression with penicillin V (250 to 500 mg orally twice daily).

Although there are no clinical trial data addressing the efficacy of suppressive antibiotic therapy in the setting of recurrent cellulitis following lymph node dissection, the practice is supported by trials that demonstrate benefit in patients with recurrent, severe bouts of lower extremity cellulitis [1-5,8].

Suppressive therapy should be tailored to individual clinical features, including microbiologic or serologic results. If suppressive penicillin fails, a resistant pathogen should be considered, such as S. mitis/oralis, which is known to sometimes be resistant to penicillin; in such cases, a non-beta-lactam antibiotic may be beneficial [9]. (See "Acute cellulitis and erysipelas in adults: Treatment", section on 'Antibiotic prophylaxis for selected patients'.)

For patients whose recurrences follow sexual activity, we suggest precoital prophylaxis (penicillin V 250 to 500 mg as a single dose prior to sex). Gynecologic evaluation may be reasonable as anecdotal experience suggests that measures such as using a water-soluble jelly during coitus may help to prevent recurrence [10]. If recurrence occurs despite the use of precoital penicillin V, we then prescribe suppressive therapy, as described above.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Skin and soft tissue infections".)

SUMMARY AND RECOMMENDATIONS

Epidemiology – Cellulitis following pelvic lymph node dissection is a rarely seen syndrome that occurs in women who have undergone local lymph node dissection for gynecologic carcinoma, specifically cervical, uterine, or vulvar carcinoma. Identified risk factors include receipt of post-operative radiation and vaginal or cervical colonization with beta-hemolytic streptococci prior to surgery. (See 'Epidemiology' above.)

Microbiology – For most patients, no pathogen is identified. When identified, most isolates are non-group A, beta-hemolytic streptococci, specifically Streptococcus agalactiae (ie, Group B Streptococcus) or Streptococcus mitis/oralis. Staphylococcus aureus is also a potential etiology. (See 'Microbiology' above.)

Clinical manifestations – Skin erythema, edema, and tenderness over the lower abdominal wall, inguinal area, and/or the proximal thigh are typical findings. Fever, chills, and systemic toxicity are often present. Average onset is 29 months following surgery. (See 'General symptoms' above.)

In some individuals with pelvic lymph node dissection, the cellulitic episode or episodes follow vaginal intercourse and is sometimes called "streptococcal sex syndrome." (See 'Timing of onset' above.)

Diagnosis – The diagnosis of cellulitis following pelvic lymph node dissection is based on the presence of clinical signs and symptoms consistent with cellulitis. Streptococcal sex syndrome should be suspected if such findings occur after vaginal intercourse. (See 'Diagnosis and evaluation' above.)

Differential diagnosis – Important considerations include necrotizing fasciitis, toxic shock syndrome, and other conditions, such as inguinal lymphadenitis, panniculitis, and appendicitis. (See 'Differential diagnosis' above.)

Antimicrobial therapy – The approach to antibiotic therapy in these patients is the same as the general approach for cellulitis. (See 'Empiric antibiotic selection' above and "Acute cellulitis and erysipelas in adults: Treatment".)

Oral regimens – Example regimens include dicloxacillin (500 mg every six hours) or cephalexin (500 mg every six hours).

For patients with purulent discharge or abscess, an appropriate regimen is trimethoprim-sulfamethoxazole (TMP-SMX; one to two double-strength tablets twice daily).

Parenteral regimens – These include cefazolin (1 to 2 g every eight hours) or nafcillin (1 to 2 g every four hours). If methicillin-resistant S. aureus (MRSA) coverage is indicated, intravenous vancomycin can be used (dosing of vancomycin is discussed in the table (table 1)).

For patients who have severe sepsis or are immunocompromised, we suggest broadening antibiotics, as discussed elsewhere. (See 'Empiric antibiotic selection' above and "Acute cellulitis and erysipelas in adults: Treatment", section on 'Selecting an antibiotic regimen'.)

Duration of therapy – The optimal duration is uncertain and should extend for at least five to six days. Therapy should be continued until clinical signs of infection have resolved. Patients with systemic manifestations quickly respond to therapy, although local skin changes may be slow. (See 'Duration of therapy' above.)

Prevention – For patients with recurrent episodes unrelated to vaginal intercourse, we suggest antimicrobial prophylaxis with penicillin V (250 to 500 mg orally twice daily) (Grade 2C) as chronic suppressive therapy. For patients with recurrent streptococcal sex syndrome, we suggest precoital prophylaxis (penicillin V 250 to 500 mg as a single dose) (Grade 2C) (see 'Prevention' above). Water-soluble lubricant jelly during coitus and other behavioral interventions may be helpful in preventing cellulitis recurrence.

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