Pyoderma gangrenosum: a rare complication of reduction mammaplasty – a case report

Introduction

Pyoderma gangrenosum (PG) is a very rare inflammatory disease of unknown etiology that affects the skin and mucous membranes. Disruption of the function of polymorphonuclear cells, which accumulate in tissues after an infectious or traumatic stimulus and release pro­teolytic enzymes that damage the tissue, is considered [1]. Typically, pustules and red nodules, which disintegrate necrotically and turn into widespread and painful ulcerations, form on the lower limbs. The diagnosis of this di­sease is clinical (ulcerations, fever, pain); the patients have increased inflammatory markers – especially leukocytes and C-reactive protein and histological exa­mination may show neutrophil infiltration. Bacterial wound infection is not found. A proper and timely diagnosis of this disease is essential for the success of the treatment. The treatment is predominantly conservative; in addition to symptomatic treatment, immunosuppressive treatment is indicated, especially with corticosteroids and cyclosporine A, while azathioprine, sulfasalazine or biological treatment (infliximab) may also be used [2]. A person’s medical history often mentions minor injuries, insect bites, etc., before the development of the sites. The occurrence of the disease at the site of the surgical wound early after the operation is described in even fewer cases. It is difficult to distinguish PG from postoperative infectious complications; however, this is absolutely essential for further treatment. It can be considered a mistake to start thinking about this disease only after several unsuccessful attempts to do necrectomy and resuture of the wound.

Case report

A 39-year-old woman underwent a reduction mammoplasty at our department in June 2019; the surgery was performed without complications, she was discharged on 2^nd postoperative day with a problem-free local finding, i.e. surgical wounds healing per primam, without signs of inflammation, afebrile. From 5^th postoperative day, the patient deve­loped fever (up to 38.5 °C) and rapidly progressing ulcerations began to appear under the breast and in vertical suture line with purulent discharge without the areola being affected. During the first examination, purulent discharge was evacuated and broad-spectrum penicillin antibiotic amoxicillin + clavulanic acid (Amoksiklav®, Lek Pharmaceuticals d.d., Ljubljana, Slovenia) was administered empirically and a culture smear was collected with a repeatedly negative result. The patient was hospitalized again with a persistent febrile condition and deteriorating local finding; intravenous penicillin antibiotic piperacillin and beta-lactamase inhibitor (Piperacillin/Tazobactam®, Sandoz, Switzerland) were administered. PG was suspected for the atypical appearance of the defects, bilateral affection and a negative finding during culture (Fig. 1). Therefore, a tissue sample was taken from the edge of the defect for histology, which described numerous neutrophil infiltrations (Fig. 2).

After consultation with a dermatologist, methylprednisolone (Solu-Medrol®, Pfizer Manufacturing, Belgium) was administered intravenously at a dose of 120 mg/day for 6 days, followed by prednisone (Prednison®, Zentiva, Czech Republic) at a dose of 50 mg/day. The effect of corticosteroid therapy was obvious both clinically and from laboratory tests, with gradual reduction of inflammatory markers from the initial value of CRP 311 mg/L and leucocytes 35×10⁹/L. Gradually, the necroses were demarcated and spontaneously separated (Fig. 3).

Antibiotics were used for 7 days only; prednisone was used as part of the corticosteroid therapy (Prednison®, Zentiva, Czech Republic) at a dose of 50 mg/day and continued for a total of 3 months with gradual reduction of the cortico­steroid dose. At the same time, regular dressings of small defects of both breasts with antiseptic non-adhesive dressing made of tulle fabric and impregnated with white soft paraffin with an active broad-spectrum antiseptic component (Bactigras®, Smith & Nephew, Great Bri­tain) were applied with following visible improvement of the defects (Fig. 4).

The patient fully healed approximately after 6 months; flat hypertrophic scars remained in the lower quadrants of the breasts (Fig. 5). During the treatment, the patient also underwent a professional immunological examination which ruled out the presence of a systemic disease that may be associated with the occurrence of PG [1].

Discussion

PG was first described by Brunsting et al. in 1930 as a rare skin disease of unknown etiology, which belongs to neutrophilic dermatoses [3]. PG is very rare as a complication following a surgery.

It mainly affects adults, most often ­between the ages of 25 and 54 years. It is more common in women [4]. The di­sease is rare in children under 15 years of age, in whom it accounts for only 4% of cases [5,6].

This condition is associated with a systemic disease in 50–70% of cases (rheumatoid arthritis, ulcerative colitis, Crohn’s disease, hematological malignancies, endocrine disorders – e.g. with an underactive thyroid gland [7], auto­immune diseases, and pregnancy in 28% of cases) [8]. Rarely, the association of PG with immunoglobulin A or M mo­noclonal gammopathy, hepatitis C, Wegener’s granulomatosis, systemic lupus erythematosus and also with human immunodeficiency virus (HIV) [9] has been reported. In about half of the cases, however, no such associated disease was detected in patients [2], which was the case of our patient as well. We verified this by retrospectively performed immunolo­gical examination of most commonly ­associated diseases. Postoperative PG has a lower association with systemic disease than other forms of PG.

The etiology of PG is unknown. Brunsting et al. hypothesized that skin ulce­rations are associated with a systemic disease that reduces resistance of the immune system. The disorder is in both humoral and cell-mediated immune responses [5,6]. In any case, PG is often ­associated with iatrogenic injury, which can be a vaccination, an injection, debridement or a surgery [6].

The average time from a surgery to the onset of the first symptoms of PG (febri­city, pain, ulceration in the wound area) is reported to be approx. 6 days. Fever and leukocytosis occur in 55% and 43% patients with PG, respectively. In case of paired organ surgery, disease propagation is bilateral in 88% [10]. An interesting thing is that neither the nipple-areola complex (NAC) nor the deeper breast parenchyma is affected if breasts are affected [4,7,8]. In our patient, only the lower quadrants of the breasts without NAC were affected. The most frequently affected parts of the body in postoperative PG are the breasts and the abdomen [4], with the lower limbs and the torso affected by other forms of PG [5]. Powell and Collins described 4 different variants of PG – ulcerative, bullous, pustular and vegetative [3].

The diagnosis of PG is tricky, the dis­­ease is often initially confused and treated as a postoperative infectious complication. Therefore, the diagnosis is indirect and based on a clinical finding, a typical histological finding and a po­sitive response to corticosteroids. Culture smears tend to be negative until the pustules ulcerate, when secondary infectious contamination of the wound may occur [5].

The treatment of the disease should be conservative while avoiding any early surgical intervention. The gene­ral the­rapy mainly includes corticoste­roid treatment. Other immunosuppressive drugs such as cyclophosphamide, aza­thioprine or cyclosporine have been used in patients with a steroid-resistant form of PG [5]. Specific targeted treatment of PG with a recombinant human interleukin-1 receptor antagonist ana­kinra has been used in case of PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum, acne) [11]. Anti-staphylococcal antibiotics can only be added to the treatment to prevent superinfection [7]. Local therapy consists of regular dressings of the defects with their change; antibacterial ointments can be used. Furthermore, intravenous steroid injections have been described in patients where systemic corticosteroids have been contraindicated [5]. The use of vacuum therapy on the defects had a positive effect on tissue perfusion and reduced secretion [12]. Hyperbaric oxy­gen therapy also improved local fin­dings and accelerated healing [5]. It has been used, for example, to stabilize defects before skin autotransplantation [13]. As stated above, no surgery (debridement, skin grafts, flap plastic surgery) should be used in the active phase of PG disease. Covering the defects with a skin graft can be successful after ­several weeks of the treatment with corticosteroids at the earliest, when the disease is in a latent phase [5].

In our patient, it was favorable for us to proceed conservatively, avoiding any surgery, and after consultation with a dermatologist, to start the treatment with corticosteroids.

Conclusion

In addition to bleeding, early complications of reduction mammoplasty include wound healing disorders or the necrosis of flaps or breast tissue. The treatment is usually surgical (necrectomy, resuture, etc.). However, surgical treatment is contraindicated in case of PG, as it may worsen further course of the di­sease. Although it is a rare complication after surgery, it is necessary to be aware of it and include it in a broader differential diagnosis. The diagnosis is indirectly based on clinical appearance, a positive response to corticosteroid therapy and also on any histological findings. In addition to early immunosuppressive treatment, it is crucial to avoid early surgical intervention in the area of the defect, which can significantly worsen the course and extent of the disease, inclu­ding the formation of difficult to reconstruct permanent consequences.

Ethical approval: All procedures performed in the case study involving human participant were in accordance with the ethical standards of the institutional research committee and with the Helsinki declaration from 1975 and its later amendments or comparable ethical standards.

Roles of authors: All authors contributed equally to preparing the manuscript.

Conflict of interests: The authors state that they have no potential conflicts of interest regarding the drugs, products or services mentioned in the case report.

Michaela Široká, MD

Department of Plastic and Aesthetic Surgery and Burn Treatment

University Hospital Hradec Králové

Sokolská 581, 500 05 Hradec Králové, Czech Republic

e-mail: michaela.siroka@fnhk.cz

Submitted: 06. 02. 2021

Accepted: 03. 04. 2021