Pyoderma gangrenosum coexisting with a myeloproliferative disorder

Introduction

Pyoderma gangrenosum is a rare disease from the group of neutrophilic dermatoses due to the large neutrophilic infiltrations on the skin and thus leading to secondary damage of vessels. Even though neutrophilic infiltrations in pyoderma gangrenosum are present in tissues bacterial infections do not play a direct role in its pathogenesis. Culture of skin and blood are always negative. Antibiotic therapy does not influence the course of the disease. It is believed that proinflammatory cytokines and growth factors take part in the process [1]. Pyoderma gangrenosum at first takes the form of a small disorder imitating a furunculus or a cyst, a small pustule, which becomes necrotic and rapidly evolves into a large ulceration. The disorder creates ulcers rapidly and spreads in a circumferential fashion, creating a large but relatively topical ulceration with a swollen necrotic ulcer bed and heaped up ruby red edges. The edges are usually undermined, blue-erythematous or violet, irregular, heaped up with presence of fistulas, partially covered with a necrotic eschar, with presence or absence of granulation tissue. Pustules are present in the active edge as well as in the bottom of the ulceration [2, 3].
The ulceration is sometimes preceded by an inflammatory infiltration or a cystic reaction [4]. The skin disorders disappear, leaving scars; the scars created in the healing process are described as sieve-like with numerous tiny holes and pits [2, 3]. One of the symptoms of pyoderma gangrenosum is pathergy – changed reactivity, which consists of appearance of skin disorders due to injuries, often very minor. Pathergy is present in 25% of pyoderma gangrenosum. If the disease is not properly diagnosed and is radically surgically treated it will progress in circumferential fashion [5]. So in a case of a suspicion of pyoderma gangrenosum it is contraindicated to conduct any procedures because they can have a negative effect on the progress of the disease. Pyoderma gangrenosum is often accompanied by systemic diseases, such as inflammatory bowel disease, autoimmune connective tissue diseases, internal organ and hematopoietic system malignancies, especially myeloproliferative disorder (MPD), acute and chronic leukemic myelosis and multiple myeloma [6, 7]. Presence of other diseases influences the progression of pyoderma gangrenosum and the prognosis of the underlying pathology influences it as well. If the underlying disease is treatable, the prognosis is good; if not, the treatment of the disease is much worse.

Objective

To present a patient with pyoderma gangrenosum concurrent with myeloproliferative disorder and the progression of the disease due to a surgical intervention.

Case report

The 78-years old woman was admitted to the Dermatologic Ward in February 2018 due to progression of an ulceration of the right buttock after a surgical intervention (fig. 1). The inflammatory infiltration of the right buttock probably occurred after an intramuscular injection of meloxicam due to spine pain. Additionally, the patient had a fever of 40°C and was weak; pneumonia of the right side was diagnosed and treated with antibiotic therapy in hospital conditions. Due to the progression of the disorder of the right buttock in the Surgical Ward in Nysa an incision was made and the muscles of the right buttock were drained. The infiltration with a progressing necrosis of the right buttock was still present and progressing. Computed tomography scan eliminated the possibility of a buttock abscess. The patient was transferred to the Dermatologic Ward. During the admission process a large ulceration with necrotic bottom and blue circumference was diagnosed on the right buttock and right hip. Three incisions after a surgical intervention were visible. Lab test showed the following deviations: increased D-dimers 1.22 g/ml (norm < 0.5), increased concentration of C-reactive protein 136.2 mg/l (norm < 5.0), elevated erythrocyte sedimentation rate 96 mm, increased procalcitonin 0.275 ng/ml (norm < 0.05), low white blood cells 3.44 × 103/μl, red blood cells 2.58 × 106/μl, heamoglobin 7.8 g/dl, platelets per citrate 25 × 103/μl without the features of thrombocytopenic purpura; differential showed increased neutrophils 72%, decreased band cells 1.2%, large platelets 8.4%. Additionally, decreased albumin and higher level of liver enzymes aspartate transaminase 34 U/l, alanine transaminase 50 U/l were noted. During previous hospitalization at the Internal Medicine Ward in January 2018 imaging procedure, i.e. USG of the abdomen and tumor markers were within the norm. The patient was consulted hematologically – further hematological diagnostics for myeloproliferative diseases is necessary. Treatment included antibiotic therapy cefepime 1.0 g i.v. every 8 hours, pulses of methylprednisolone 500 mg i.v./day for 5 days, prednisone dose of 40 mg/day and topical glucocorticosteroid ointments and specialized dressings resulting in an improvement of morphotic parameters, general and local condition (fig. 2). The patient was discharged in good condition with an indication to broaden the hematological diagnostics for myeloproliferative diseases. The patient is constantly monitored by dermatological and hematological clinics, where further regression of the disorder is being observed (fig. 3).

Discussion

Pyoderma gangrenosum is a neutrophilic dermatosis with unclear etiology. Common concurrence of pyoderma gangrenosum with autoimmune disorders and presence of pathergy suggest a role of the immunological system in the disease [8]. Involvement in the pathophysiological mechanism of the disease has been attributed to cellular and humoral immunity disorders, as well as defective function of monocytes and neutrophils [9–11]. In 50% of cases the disease is preceded by a small injury, such as a needle prick or an insect bite (pathergy symptoms). In the case described above pyoderma gangrenosum progressed probably after an injection of an anti-inflammatory drug into the right buttock. Misdiagnosis of pyoderma gangrenosum is nothing surprising (over 10%) [12].
Pyoderma gangrenosum is often misdiagnosed as an infection of a post-surgical wound, and the medical procedures (mechanical cleaning, cutting the wound, drainage) worsen the disease process in the pathergy mechanism, whereas antibiotic therapy and cleaning of the wound do not stop rapid growth of the ulceration [8, 13]. In our patient, surgical interventions, such as incisions and draining of the right buttock muscles, caused spreading of pyoderma gangrenosum. In over 50% of cases pyoderma gangrenosum is accompanied by systemic disease. Non-specific enterocolitis is the most common accompanying disease. In around 7% of cases rheumatic diseases are present, whereas in around 1% of pyoderma gangrenosum cases hematological diseases develop, e.g. leukemia, polycythemia, myelofibrosis, essential thrombocytosis, multiple myeloma, most often an acute and chronic leukemic myelosis, whereas myeloproliferative disorder is not so often connected with pyoderma gangrenosum [14]. Myeloproliferative disorder mainly occurs in 60-year-old and above patients and usually causes acute cytopenia. We distinguish 5 basic types of myeloproliferative disorder, which differ in cytological features and the number of blasts in bone marrow smears and peripheral blood. It transforms into acute leukemic myelosis in 6% to 37% of patients with myeloproliferative disorder. Different skin disorders can occur with myeloproliferative disorder. We distinguish typical and atypical disorders in myeloproliferative disorder. The typical ones are an effect of an invasion of the skin by malignant hematopoietic system cells. Clinical symptoms include papules, phymas or nodules. The atypical ones include infections, vessel inflammation and neutrophilic dermatoses, including pyoderma gangrenosum [15]. The occurrence of dermatosis in a patient treated for a hematopoietic system disorder usually means a recurrence of a disease or its severe transformation and is a bad prognostic sign. Neutrophilic dermatoses, especially when they recur, can precede the development of myeloproliferative disorder by 2–8 years [16]. Due to the rarity of the disease and an uncertain etiology there are no treatment standards in the literature, and the choice of treatment depends on the clinical image, concurrent diseases and the general condition of a patient [17]. Usually, systemic therapy with a topical treatment, using, among others, systemic glucocorticosteroids with antibiotics, tacrolimus, cyclosporine, sulfasalasine, 10% silver nitrate, 1% sodium cromoglicate, is recommended. In the first-line treatment many authors proposes systemic glucocorticosteroid, prednisone 0.5–1.0 mg/kg body mass/day or methylprednisolone 0.8 mg/kg body mass/day p.o., and in a rapidly developing disease pulses of methylprednisolone of 500 mg i.v. for 3–5 days. The steroid treatment is then continued with, e.g. prednisone 40–60 mg/day for around 5–6 months, and then the dose is gradually reduced [18]. In the described patient, due to the rapid progression of the ulceration and concurrent hematological disorders, it was decided to implement pulses of methylprednisolone i.v. 500 mg/day for 5 days, then prednisone 40 mg/day and topical glucocorticosteroid ointments and specialized dressing, which resulted in an improvement of morphotic parameters, achieving rapid improvement of the local condition and hematological parameters. Systemic glucocorticosteroid was beneficial not only in reducing the ulceration but also in improving the hematological parameters of myeloproliferative disorder.

Conclusions

Pyoderma gangrenosum is often accompanied by systemic diseases, which is why a holistic approach to a patient and looking for concurrent diseases and their treatment are important. Correct diagnosis of the disease prevents unnecessary surgical interventions, which more often than not lead to ulceration progression. Due to the lack of treatment standards, the choice is individual and depends upon the severity of the skin disorders, general condition of a patient, and concurrent diseases. In the presented patient the morphological changes and pathergy pointed to pyoderma gangrenosum, and the morphotic image and broad hematological diagnostics pointed to the concurrence of myeloproliferative disorder. The implementation of glucocorticosteroid pulses led to a quick improvement of the clinical condition. The patient required constant dermatological and hematological monitoring.

Conflict of interest

The authors declare no conflict of interest.

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