A non-infectious “infection” after a cesarean delivery

Scenario:

A 23-year-old woman with a history of hidradenitis suppurativa presented for elective repeat caesarean section at 39 weeks and 0 days of gestation. Her previous caesarean delivery was notable for a 6-month recovery secondary to wound infection requiring surgical debridement, prolonged use of vacuum-assisted closure (VAC), and multiple antibiotic treatments.

Her cesarean delivery was uneventful, and the decision was made to empirically place a Prevena closed-incision VAC.

In the first postoperative days, the patient complains of progressive incisional pain. She was put on triple antibiotic therapy due to febrile morbidity and a diagnosis of endometritis.

On the ninth postoperative day, wound dehiscence and respiratory distress lead to intensive care admission. Two abdominal washouts do not improve healing (Figure 1). All wound cultures are negative and microscopy reveals no bacteria, only an abundance of neutrophils. An autoimmune test is negative.

What is going on?

Pyoderma gangrenosum (PG) is a chronic, rare and recurrent ulcerative skin disease with an incidence of 3 to 10 cases per million in the general population.1 It is often mistaken for an infection because of the impressive sores and marked purulence. Repeat negative cultures combined with an inability to respond to standard wound care and antibiotics should prompt inclusion of the diagnosis in the differential. Clinically, a blue to purplish rolled wound edge is classic but not pathognomonic. Therefore, tissue pathology can often help solidify the diagnosis. In this case, the tissue obtained from the lavage was stained with standard hematoxylin and eosin, revealing a dense neutrophilic infiltrate and the absence of bacteria.

PG disproportionately affects women between the ages of 20 and 50, and about half of patients have an associated pro-inflammatory disease such as inflammatory bowel disease (IBD), hidradenitis suppurativa, or rheumatoid arthritis.2 Associated malignancies include acute and chronic myeloid leukemia and monoclonal IgA gammopathy. Between 1.5% and 5% of patients with IBD develop PG.3

The pathophysiology of PG is poorly understood; however, family reunification indicates a likely genetic predisposition. Pathergy (defined as an exaggerated skin lesion following minor trauma that may be resistant to healing) is noted in approximately 15% of cases, as illustrated in this patient.

Ulcerative PG is the most common subtype of PG, usually beginning on the lower limb as a tender, indurated erythematous papulopustule that ulcerates over weeks to months, leaving full-thickness necrosis with a purulent base and irregular metallic gray border. PG bullous lesions are more superficial and are associated with leukemia or polycythemia vera. The vegetative PG is the least aggressive variant; he has high cribriform ulcerations and is not related to systemic disease. Aggressive surgical debridement leads to paradoxical pathergy and worsening of the wound.

The development of lesions is usually rapid and the pain may be disproportionate to the onset of ulceration. Fever and systemic symptoms may accompany this process.4 This patient had a typical clinical course, with postoperative dehiscence and systemic symptoms including respiratory distress.

Differential and initial assessment

Although there are no validated criteria for the diagnosis of PG, a wound biopsy to assess a neutrophilic response and exclude other conditions is recommended. This specimen should include the edge of the wound and the base of the ulcer for permanent histopathology (formaldehyde). The sensitivity of wound culture is insufficient for diagnosis because colonization can be misinterpreted as causal. Bacterial, mycobacterial, and fungal tissue cultures should be obtained to exclude an infectious etiology.

Laboratory studies to support the diagnosis may include erythrocyte sedimentation rate and C-reactive protein, but low specificity makes usefulness questionable. Since approximately 50% of patients with PG have Crohn’s disease or ulcerative colitis, a thorough gastrointestinal systems examination and serologic testing for fecal calprotectin should be performed.2 The clinical evaluation of a history of hidradenitis suppurativa should be explored.

About 10% of cases are associated with leukaemia, and the assessment of a monoclonal gammopathy with protein and urine electrophoresis could be considered; some authors recommend Bence Jones protein analysis.5 Tests for hepatitis, syphilis and HIV are reasonable. Since approximately 30% of patients have coexisting arthritis, it is reasonable to consider evaluation with rheumatoid factor and an anti-cyclic citrullinated peptide. A hypercoagulability assessment should be considered if a review of the systems warrants it.

Initial management by an obstetrician

Considering that it is a rare diagnosis, it is often absent from the differential. Even more difficult is to redirect management from antibiotics to anti-inflammatories. Meticulous surgical techniques are essential, especially in a patient with a known or suspected history of PG. We recommend closing the incisions with sutures rather than staples and considering the use of preoperative steroids to minimize the risk of pathergy. If a lesion develops, initial treatment is to optimize wound care, minimize pathergy for subsequent surgery, and initiate topical or intralesional treatment as described below.

First-line treatment for small lesions without systemic symptoms involves topical anti-inflammatories, including corticosteroids, tacrolimus, and dapsone. These wounds are indeed mucosal sites, and it should be noted that systemic absorption of these drugs has been detected. In the absence of systemic symptoms, small wounds can be treated with intralesional steroids at a concentration of 10 mg/mL at the wound edge. Topical clobetasol, tacrolimus, and dapsone have been used with anecdotal success.

Consider tacrolimus levels for larger wounds requiring frequent application. When using dapsone topical, watch for common adverse effects (AEs) of nausea, vomiting, decreased appetite, blurred vision, tinnitus, and insomnia.

Sores that worsen or do not improve with a topical regimen may require systemic treatment such as high-dose corticosteroids or immune modulators.

Glucocorticoids, such as prednisone, are usually given in high doses until all lesions have healed, but may be continued at lower doses as maintenance therapy to prevent recurrences. Systemic cyclosporine may be an alternative for patients who cannot tolerate glucocorticoid therapy, but the use of other therapies such as dapsone and minocycline have also been described.6

There is a trend towards biologics as first-line therapy, particularly of the tumor necrosis factor α class, including infliximab and adalimumab, as they have a rapid response and have an AE profile tolerable and a limited duration of use.

The association with pathophysiological similarities to hidradenitis suppurativa, inflammatory bowel disease, and psoriasis further supports this practice. However, cost is often a throughput limiting factor. Although a course of adalimumab of 3 to 6 months is expensive, we propose that it costs less than several hospital stays for debridement, wound VACs, parenteral antibiotics, wound care and alteration of daily functions of the patient.

In this patient, without clinical improvement and negative infectious workup, the differential diagnosis was extended to PG. A wound biopsy confirmed the presence of an overwhelming neutrophil response with a focal area of ​​necrosis, which may be consistent with PG (Figure 2). The patient was put on systemic oral corticosteroids and her symptoms improved rapidly. She was discharged from the hospital 48 hours later, with a prednisone cone with a standard VAC in place. One week later, a significant improvement in the incision was noted (Figure 3). Complete healing occurred 6 weeks after discharge from hospital.

The references

  1. Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G. Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol VenereoL. 2009;23(9):1008-1017. doi:10.1111/j.1468-3083.2009.03199.x
  2. Huang BL, Chandra S, Shih DQ. Cutaneous manifestations of inflammatory bowel disease. Before Physiol. 2012;3:13. doi:10.3389/fphys.2012.00013
  3. Davis MDP, Moschella S. Neutrophilic dermatoses. In: Bologna JL, ed. Dermatology. 4th ed. Elsevier; 2018:459-463.
  4. George C, Deroide F, Rustin M. Pyoderma gangrenosum – a guide to diagnosis and management. Clin Med (London). 2019;19(3):224-228. doi:10.7861/clinmedicine.19-3-224
  5. Tolkachjov SN, Fahy AS, Wetter DA, et al. Postoperative pyoderma gangrenosum (PG): the 20-year Mayo Clinic experience from 1994 to 2014. J Am Acad Dermatol. 2015;73(4):615-622. doi:10.1016/j.jaad.2015.06.054
  6. Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol. 1996;34(3):395-409; questionnaire 410-412. doi:10.1016/s0190-9622(96)90428-4

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