Pyoderma gangrenosum of the breast 17 years after breast cancer treatment

Abstract

We present a case of pyoderma gangrenosum (PG) affecting the breast of a 74-year-old woman, with a history of breast cancer treated with breast conserving surgery and adjuvant radiotherapy 17 years prior. She presented to the hospital with worsening breast ulceration, after a punch biopsy was performed at the site. She had surrounding cellulitis and concurrent infection to that breast which required antibiotics. The ulceration persisted even after treatment, and incisional biopsies of the area of ulceration confirmed the diagnosis of PG. Her condition was managed effectively with the use of immunosuppressive therapy, and she continued to display a good clinical response 2 months post discharge from the hospital.

Background

Pyoderma gangrenosum (PG) of the breast is difficult to diagnose. Although it is seldom encountered, surgeons should entertain this diagnosis in patients presenting with a severely painful ulcer which is progressing. Our case highlights the importance of a multidisciplinary approach to help facilitate a diagnosis. Prompt treatment with immunosuppressive therapy and appropriate wound care can help reduce patient morbidity. Prolonged treatment is often required with complete wound healing occurring months to years after the initial diagnosis.

This case is important as it highlights the complexities of treating PG in a patient with preceding cellulitis and infection. It also highlights the challenges faced by patients who have previously had radiation therapy which predisposes individuals to fibrosis, oedema and ischaemia, all of which can impair wound healing and lead to chronic ulceration.

Case presentation

A 74-year-old woman was admitted to hospital with worsening cellulitis of her left breast. This was on a background of left breast conserving surgery for cancer followed by adjuvant radiotherapy in 2002. Her medical history included chronic kidney disease secondary to hypertension, gout, psoriasis, atrial fibrillation and recurrent papillary bladder cancer. She is an ex-smoker and is allergic to penicillin.

She originally presented with an 8-week history of a non-healing ulcer in her left axilla measuring 4×1.5 cm (figure 1). Two punch biopsies were taken: one at the site of ulceration and the other at the 12 o’clock position of the left breast. The axilla biopsy showed ulcerated skin containing mixed inflammation in the superficial dermis, consistent with previous radiation therapy. There was no evidence of malignancy, bacteria, fungi or mycobacterium. Histopathology of the 12 o’clock punch biopsy showed dermal fibrosis with fat necrosis, again consistent with prior radiotherapy. There was focal calcification in the subcutis near the base of the specimen, with no malignant features identified. On mammography, stable left dystrophic calcification was noted, with no suspicion of new malignancy demonstrated.

Figure 1.

Original ulcer to left axilla.

On subsequent review, the patient’s condition had worsened with surrounding cellulitis and progression of the ulceration, with relative sparing of the nipple–areolar complex (figure 2). Asides from pain, she remained clinically well with no fevers or systemic signs of sepsis. Her white cell count (WCC) was 12.3×10⁹/L and C reactive protein (CRP) was 74. She was admitted to hospital for intravenous cephazolin and wound care. An ultrasound showed no drainable collection, but diffuse skin thickening, soft tissue hyperaemia and echogenicity within the left breast likely representing infection/inflammation. A presumptive diagnosis of a radionecrotic ulcer with surrounding cellulitis was made. Despite intravenous antibiotics, the patient deteriorated with fevers, worsening inflammatory markers (WCC 22×10⁹/L, CRP 343) and acute kidney impairment. Her wound culture had heavy growth of skin flora including enterococci. Blood cultures were negative. In consultation with the infectious disease unit, vancomycin was added. Given the atypical presentation, she was discussed with the dermatology team, with a number of investigations ordered at this point. Mycobacterium ulcerans PCR was negative as was serology for hepatitis, HIV, syphilis, stongyloides, tuberculosis and varicella zoster thus excluding other causes of infection which could be contributing to the patient’s condition. Tests conducted to exclude underlying auto-immune conditions including anti-neutrophil cytoplasmic antibodies (ANCA), antinuclear antibody (ANA), extractable nuclear antigens (ENA), erythrocyte sedimentation rate (ESR), C3/C4, direct coombs, antiphospholipid antibodies, faecal calprotectin, rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies were also negative. A chest X-ray (CXR) excluded underlying infection/metastasis while a CT chest demonstrated changes consistent with previous surgery as well as calcification. An incisional biopsy was recommended at this point to investigate for other causes of ulceration including sweets syndrome, PG, panniculitis and vasculitis.

Figure 2.

Progressive ulceration of the left breast.

The patient’s condition continued to deteriorate despite being on 5 days of intravenous cephazolin and 1 day of vancomycin. She developed rapid atrial fibrillation (AF) and continued to spike temperatures up to 39°C. Her antibiotic coverage was broadened to include ceftriaxone and metronidazole for 1 day but this was subsequently changed to meropenem and vancomycin only. An incisional biopsy was facilitated at this point with half of the tissue sent as a fresh specimen for bacterial microscopy, culture and sensitivity (MCS), acid fast bacilli (AFB), deep fungal MCS and pan-mycobacterial PCR. The other half was sent in formalin for histopathology. In recovery, the patient became hypotensive and required a metaraminol infusion. She was transferred to the intensive care unit for ongoing management. She continued to have marked ulceration and cellulitis of the left breast (figure 3). The patient spent 5 days in the intensive care unit with her WCC peaking at 67×10⁹/L. She was able to be weaned off norepinephrine and was discharged back to the surgical ward. Wound cultures grew a fully sensitive Staphylococcus aureus and Enterococcus faecalis and she was managed on meropenem and clindamycin at that point. Her condition continued to improve, with a reduction in her inflammatory markers. She was de-escalated to oral clindamycin at day 12 of her admission and then received de-sensitisation therapy with amoxycillin before being transitioned to a course of Augmentin DF for 5 days. Her cellulitis had markedly improved at this point and there was no further progression of her breast ulceration.

Figure 3.

Worsening necrosis, ulceration and erythema following two incisional biopsies.

Investigations

She was diagnosed with PG on day 14 of her admission, based on the clinical presentation and incisional biopsy results, which displayed marked neutrophil infiltration, alongside tissue necrosis and dense acute abscess formation. Specimens contained widespread epidermal ulceration, with evidence of secondary vasculitis. There was no evidence of dysplasia or malignancy which were key differential diagnosis that warranted exclusion. No bacterial or fungal organisms were identified.

Treatment

Treatment for PG was commenced on day 15 when her WCC was normal and CRP was 46. This consisted of 50 mg prednisolone daily, 500 mg mycophenylate BD (twice a day) and minomycin 50 mg mane and 100 mg nocte. Ciclosporin was not used due to the patients underlying chronic kidney disease (CKD). Unfortunately, the patient developed progressive pancytopenia. Haematology attributed this to the mycophenylate. The patient was also diagnosed with monoclonal gammopathy of undetermined significance (MGUS) IgK variant given her serum protein electrophoresis and serum free light chain results. This condition is not associated with PG nor were there any other features on blood films or haematological testing to suggest underlying haematological malignancy which could account for this condition.

The patients Mycophenylate dose was reduced to a daily dose, but her pancytopenia continued to progress so it was later ceased. Intravenous immunoglobulin (IVIg) at 2 g/kg was given in three divided doses over the next 3 days. All blood counts stabilised and she was able to be discharged home on day 27 on oral prednisolone and minocycline.

Outcome and follow-up

On discharge, she was regularly followed up in the dermatology, surgical breast and plastic surgery outpatient clinics, while daily dressing changes were facilitated by district nursing services. In the 2 months post discharge, she has received a further two courses of IVIg with the Prednisolone dose weaned over this time. This has led to an excellent clinical response, with a marked reduction in her breast ulceration.

Discussion

PG is a rare condition, with the incidence estimated to be between three and ten per million per year.¹ First described in 1916, by Brocq and later by Brunsting et al in 1930, it was originally described as being infectious in aetiology; however, it is now characterised as a non-infectious neutrophilic dermatosis.^{2 3} Although the pathophysiology behind this condition is still unknown, a dysfunctional immune response is believed to play a role in genetically predisposed individuals.⁴ Individuals with underlying haematological diseases, inflammatory bowel disease and rheumatoid arthritis are particularly at risk, with 50%–78% of reported cases of PG linked to these conditions.^{1 5} There is also an association between PG and previously diagnosed solid organ malignancy.⁶

PG initially presents as sterile pustules that rapidly progress into painful ulcers of variable depth and size with undermined violaceous borders.⁵ Histologically, lymphocytic vasculitis is found peripheral to the area of ulceration, while neutrophilic infiltrate and abscess formation is more prominent centrally.³ While many of these ulcers are usually located in the lower extremities, they can occur at any site. The breast is an unusual site for PG, with only 43 reported cases in the literature, 70% of which emerged after breast surgery.⁷ When they do occur in the breast, the overwhelming majority occur after surgical intervention.⁸

PG of the breast is difficult to diagnose due to the lack of diagnostic laboratory or histological findings.⁷ Prompt recognition allows for effective treatment options to be instituted which can lead to a good clinical response. Treatment involves appropriate wound care, administration of corticosteroids and other systemic immunomodulatory drugs for those who fail to respond to first line therapy.^{5 9} Prolonged treatment is often required with complete wound healing occurring months to years post the initial diagnosis, with relapses not uncommon.⁵ Surgical debridement should be avoided as it can lead to pathergy which can further exacerbate the ulcerative process.⁵ This concept was highlighted in our case, whereby the patients original punch biopsy and subsequent incisional biopsy lead to a worsening of her condition.

Our case presented without a recent surgical insult which is rare for cases of PG affecting the breast.^{7 8} There have been reported cases in the literature, whereby PG developed with no preceding insult, however our case is unique in that the patient had a preceding infection.^{7 10–12} To our knowledge, only one other case reported positive growth on wound swabs in a patient with no preceding surgical insult; however, this was only identified on repeated wound swabs.¹³ Our case also demonstrated the process of pathergy, whereby the punch biopsy taken of the original ulcer led to rapid and marked ulceration of the breast. Our case occurred in a patient previously treated for breast cancer 17 years prior, an association not previously reported in the literature. Radiation therapy can lead to long term effects, commonly oedema and fibrosis which can present months to years after treatment.¹⁴ It can cause relative ischaemia in that area as small arteries and arterioles are predisposed to thrombosis or obstruction.^{15 16} This can lead to skin breakdown and ulceration, with poor wound healing and subsequent infections to the area often being chronic and difficult to treat.^{15 16}

Overall, our case was challenging to manage, as the patient’s concurrent infection and overlying cellulitis warranted treatment in its own right. Once this was adequately managed with antibiotics, we were only then able to entertain the idea of PG. Once identified, the patient received the appropriate treatment and displayed a good clinical response.

Learning points.

• Pyoderma gangrenosum of the breast is rare, but should be considered in patients with painful and progressive skin ulceration.

• Treatment can be challenging in the setting of sepsis, as it can be difficult to determine when to commence immunosuppressive therapy.

• It is important to avoid further insults to the area of ulceration as this can lead to the phenomenon of pathergy.

• Treatment can be made more difficult in individuals exposed to radiation therapy. Radiotherapy can lead to long term sequelae months to years after treatment, leading to skin breakdown and ulceration. Poor wound healing and subsequent infections to the area are often chronic and difficult to treat. Our case is the first in the literature to report such an association.