Facial Pyoderma Gangrenosum – Presentation of Two Clinical Cases and Literature Review

Pyoderma gangrenosum (PG) is a rare chronic neutrophilic dermatosis characterized by a distinct clinical course and typical morphology of skin lesions [1]. In approximately half of the cases, PG is associated with a systemic disease, most commonly inflammatory bowel disease, arthritis, or hematologic proliferative disorders. It can also present as a cutaneous manifestation of rare, genetically determined autoinflammatory syndromes [2]. In the medical literature, various types of PG are distinguished, including ulcerative (classic), pustular, bullous, vegetative, peristomal, genital, and other rarer variants [2]. Some of them exhibit stronger associations with concurrent systemic diseases. For example, there are literature reports of pyostomatitis vegetans, a chronic vegetating variant of pyoderma affecting the mucous membranes of the lips and cheeks, often presenting with large papillary plaques and pustules. This form of PG is typically seen in patients with inflammatory bowel disease [3], as is peristomal pyoderma [4].
The primary lesion typically presents as a tender pustule, nodule, or bulla on an erythematous or violaceous base. Subsequently, rapid progression of the lesion occurs, with the development of necrosis, leading to the formation of an ulcer with elevated, undermined, gray-violaceous borders. The number of ulcers may reach approximately a dozen. Interestingly, coexisting sterile neutrophilic infiltrates in internal organs are also possible [2]. The lesions are predominantly found on the skin of the lower legs [5], with other areas of the body being less frequently affected. In rare cases, the disease may manifest in the head and neck region.
The study aims to present 2 extremely rare cases of patients with pyoderma gangrenosum localized to the face, with coexisting inflammatory bowel disease. The available literature on this topic is also reviewed, with particular emphasis on the relationship between pyoderma gangrenosum and inflammatory bowel diseases, as well as available therapeutic options.
Case 1. A 79-year-old female patient, diagnosed with ulcerative colitis 4 years earlier, was admitted to the Dermatology Department for further diagnostic evaluation and treatment optimization of a progressive ulcer located on her forehead. The lesion initially presented as a gray-blue nodule on the skin of the forehead, which rapidly enlarged over 3 months into an extensive ulcer involving the forehead and the nasal root. The patient had previously been treated at the surgical outpatient clinic, where the etiology of the lesion was suspected to be infectious.
The treatment regimen included clindamycin, topical hyaluronic acid with micronized silver and vitamin E, as well as fusidic acid cream and silver dressings. Despite this treatment, the ulcer continued to progress without improvement. Consequently, a biopsy was performed at the surgical outpatient clinic to establish the etiology of the lesion and exclude a neoplastic origin. Histopathological examination revealed a purulent inflammatory infiltrate with granulation tissue.
Upon admission to the Department, a large ulcer measuring 12 × 15 cm was observed, involving the forehead and the nasal root, with a significant amount of necrotic tissue and purulent discharge in the base. The border of the ulcer was raised and violaceous (fig. 1 A). Due to the lesion’s location, a computed tomography scan of the paranasal sinuses was performed revealing no abnormalities. During the patient’s stay in the Department, the initial treatment involved intravenous antibiotic therapy with piperacillin/tazobactam. However, despite this intervention, the ulcer continued to progress. On the third day of hospitalization, intravenous methylprednisolone at a dose of 60 mg/day was added to the treatment regimen. By the 6^th day of hospitalization, significant improvement in the patient’s ulceration was observed. Given the simultaneous exacerbation of ulcerative colitis (manifested by numerous bloody stools), mesalazine was incorporated into the treatment. On the 13^th day of hospitalization, following stabilization and initial regression of the ulcer, the patient was discharged with instructions to continue oral steroid therapy.
The patient was re-hospitalized in the Department within 4 weeks, at which time significant reduction in the extent of the ulcer and flattening of its edges were observed (fig. 1 B), along with remission of gastrointestinal symptoms. The doses of systemic glucocorticosteroids were gradually tapered, and infliximab as an intravenous infusion at a dose of 300 mg was introduced into the treatment regimen. Infliximab was administered at 8-week intervals, resulting in nearly complete healing of the ulcer and sustained remission of the patient’s intestinal symptoms. After 6 months (fig. 1 C), complete remission of skin and intestinal lesions was observed. Consequently, a decision was made to discontinue infliximab therapy and initiate treatment with adalimumab administered as subcutaneous injections at a dose of 40 mg every 2 weeks.
The patient remains under ongoing supervision at the Department’s dermatology outpatient clinic, where she continues treatment with adalimumab. She shows no signs of pyoderma recurrence and exhibits no clinical symptoms of ulcerative colitis.
Case 2. A 27-year-old man with untreated Crohn’s disease was admitted to the Dermatology Department with suspected facial pyoderma gangrenosum. The skin lesions first appeared 3 months earlier as small pustules on the cheeks, which quickly progressed to deep ulcers.
Upon admission, the patient presented with bilateral facial ulcers extending from the tear troughs to the nasolabial folds. The left-sided lesions also involved the lateral nasal surface and lower eyelid region. The edges of the ulcers were infiltrated, uneven, with a papillary surface, and the bases of the lesions contained a large amount of purulent discharge and fibrin (figs. 2 A, B). The skin on the patient's back revealed scattered perforated ulcers, each several millimeters in size (fig. 2 C). Correlated with the clinical presentation, histopathological analysis of the skin biopsy suggested that the microscopic findings could be consistent with pyoderma gangrenosum. In view of the location and morphology of the skin lesions, diagnostic tests for granulomatosis with polyangiitis were also conducted, but the results were negative.
Initially, the patient received systemic steroid therapy using methylprednisolone at a dose of 1 mg/kg of body weight. Due to the inadequate clinical response, on the 11^th day of hospitalization, a decision was made to initiate intravenous pulses of methylprednisolone (at a total dose of 2000 mg), followed by continued treatment with smaller oral doses. Following 3 weeks of hospitalization and notable clinical improvement, the patient was discharged with instructions to continue treatment with oral steroids and oral cyclosporine at a dose of 3 mg/kg of body weight per day. During outpatient check-ups 4 months later, recurrence of skin lesions was observed following a reduction of steroids to 40 mg of prednisone per day, despite the use of cyclosporine (figs. 2 D, E).
Consequently, infliximab at a dose of 400 mg, administered in two divided doses, was added to treatment. At the follow-up examination 8 weeks after the first dose, significant regression of the skin lesions was observed. Infliximab therapy was maintained for an additional 30 weeks, resulting in further improvement of the local condition (figs. 2 F, G) and sustained remission of gastrointestinal symptoms.
The patient was referred to a plastic surgery clinic for correction of left lower eyelid ectropion, which developed secondary to ulcer infiltration with subsequent fibrotic changes during healing.
To date, only a few cases of facial pyoderma gangrenosum have been reported in the literature. The diagnosis is typically based on a characteristic clinical course, exclusion of infectious and neoplastic etiologies, histopathological findings consistent with PG, and a rapid response to immunosuppressive therapy [6]. While the concurrent presence of a systemic inflammatory disease may support the diagnosis, it is not a mandatory criterion. Notably, some studies suggest that a significant proportion of facial PG cases may occur without any associated systemic conditions [7].
Seok et al. reported a case of a 27-year-old female patient with pyoderma gangrenosum on the skin of the left temple, who, like our patients, had coexisting inflammatory bowel disease [8]. The skin lesions exhibited typical clinical presentation and progression. In the reported case, the patient initially developed a small pustule that rapidly evolved into a large ulcer with a raised red-purple border. Systemic corticosteroid therapy was initiated, leading to rapid clinical improvement observed within 1 week. Subsequently, the patient successfully underwent reconstruction with a free skin flap. However, it is important to note that surgical intervention is not the treatment of choice for the condition, as approximately 20–30% of patients with PG exhibit symptoms of pathergy. Consequently, surgical procedures may exacerbate existing lesions, trigger disease recurrence, or induce new ulcerations [9, 10]. Nonetheless, in cases involving deep, complicated ulcers, surgical intervention may become unavoidable. When surgery is required, optimal disease control should be achieved through immunosuppressive treatment.
Jiang et al. reported a case of a patient with severe, treatment-resistant multifocal pyoderma gangrenosum, primarily affecting the face and extending to all four limbs [11]. The patient received intravenous methylprednisolone, cyclosporine A, antibiotic therapy, and colchicine, but these interventions proved ineffective. Additionally, glucocorticosteroid treatment was complicated by the development of vertebral compression fractures.
The disease had a severe course, resulting in destruction of the nasal septum, maxillary sinus abscess formation, and facial nerve palsy. After undergoing the necessary surgical treatment, the patient was successfully treated with a combination of prednisone and infliximab. Biological treatment proved to be the most effective option for the patient; however, its use was limited due to economic constraints. The patient had no prior medical history of clinically overt inflammatory bowel disease. Nevertheless, primary sclerosing cholangitis (PSC) was diagnosed, a condition that is closely associated both pathogenetically and epidemiologically with inflammatory bowel diseases. In fact, some authors regard PSC as an extraintestinal manifestation of inflammatory bowel diseases. In such cases, bowel disease may remain undiagnosed due to its subclinical course. Confirming gastrointestinal inflammation requires an endoscopic or histopathological examination [12].
The etiopathogenesis of pyoderma gangrenosum is complex and not yet fully elucidated. A pivotal role in the formation of ulcers is thought to be played by immune system dysregulation. Histopathological examination of a biopsy specimen obtained from the edge of the ulcer commonly reveals extensive granulocytic infiltration within the dermis, with no evidence of vasculitis. Consequently, early research on disease pathogenesis focused on neutrophil chemotaxis disorders and excessive integrin-endothelium interactions promoting neutrophil migration from blood vessels into the skin. However, it remains unclear whether neutrophil dysfunction in PG is primary or secondary to other causes, such as inflammasome activation and overexpression of proinflammatory mediators, including TNF-α, IL-1β, and IL-8 [13, 14]. In addition to the abundant granulocytic infiltration at the ulcer edges, T cell infiltrates are observed. These cells may further stimulate neutrophil chemotaxis through the secretion of cytokines such as IL-8 and TNF-α. An imbalance in the Th1/Th17 lymphocyte ratio has also been reported, along with hyperactivation of the inflammasome – a key component of innate immunity. This dysregulation leads to excessive IL-1β production, which in turn increases TNF-α and IL-8 production. Material collected from the lesions shows elevated expression of inflammatory mediators including TNF-α, IL-8, IL-17, MMP2, MMP9, and VEGF [14].
Systemic treatment of PG is typically based on steroids, cyclosporine, and TNF-α inhibitors. For isolated small lesions (≤ 4 cm²) with a less aggressive course – or when systemic treatment is contraindicated – topical therapy with glucocorticosteroids and calcineurin inhibitors may be considered [5, 15]. Reports in the literature suggest that TNF-α inhibitors should be considered as the treatment of choice for patients with PG and coexisting systemic inflammatory disease, due to their mechanism of action and the added benefit of systemic disease control [15]. By blocking neutrophil chemotaxis mediated by this cytokine [16], these agents effectively disrupt the cascade of pathogenic processes within the lesions, inducing ulcer regression and promoting healing [17]. TNF-α inhibitors provide additional therapeutic benefits in patients with coexisting inflammatory bowel disease by inducing rapid T-cell apoptosis (< 24 hours) in the mucosal lamina propria. This mechanism helps suppress the gastrointestinal inflammatory cascade, promoting disease remission [18]. The response to treatment of PG with infliximab and adalimumab in patients with coexisting inflammatory bowel disease is nearly complete, exceeding 90%, which significantly surpasses the therapeutic efficacy of other available modalities [19].
There is no single test that can definitively confirm a diagnosis of PG. Various diagnostic criteria for PG have been proposed in the literature [5]. In practice, the diagnosis of PG relies on recognizing its characteristic clinical presentation and ruling out other potential causes of non-healing ulcers, such as infections, vasculitis, neoplastic diseases, or vascular ulcers. Rapid suppression of the inflammatory process and induction of remission following the initiation of immunosuppressive treatment further confirm the suspicion of PG. The first observable sign of remission is flattening of the lesion’s borders. Previous studies have also documented the so-called Gulliver’s sign – a pattern of epithelialization that begins at the lesion’s edge and progresses inward, forming epithelial protrusions [20]. This sign marks the onset of ulcer regression and the beginning of the healing phase.
Upon complete resolution, the disease typically leaves behind distinctive cribriform, atrophic scars, frequently accompanied by areas of discoloration. Moreover, typical histopathological findings of granulocytic infiltration (with or without a lymphocytic component) in the absence of features of vasculitis can provide valuable evidence supporting the clinical diagnosis of PG.
For dermatologists, diagnosing a condition with a characteristic course and typical localization on the lower limbs should not pose a challenge; however, dermatology specialists are usually not the first physicians to evaluate patients with PG. Moreover, the presence of skin lesions in atypical locations, such as the face, can complicate diagnosis even for experienced clinicians. In a retrospective analysis of 219 cases of PG involving the head and neck region, dermatologists accurately diagnosed the condition in 58.1% of cases, whereas physicians from other specialties achieved a correct diagnosis in only 33.3% of cases. The condition was frequently mistaken for an ulcer of infectious etiology [21]. Facial involvement in PG is also uncommon among patients with inflammatory bowel disease, occurring in only approximately 4% of all PG cases in this population [22].
A lack of awareness about this condition among physicians may lead to inappropriate referrals to surgical, infectious disease, or internal medicine departments or outpatient clinics, potentially delaying accurate diagnosis and the initiation of effective treatment. Primary care physicians should be sufficiently familiar with PG to ensure timely referrals to specialists experienced in managing the disease. In patients presenting with non-healing ulcers in the head and neck region, the presence of concomitant systemic inflammatory disease – particularly bowel involvement – should raise diagnostic suspicion. In such rare cases, close interdisciplinary collaboration between dermatologists and gastroenterologists may prove invaluable for ensuring optimal therapeutic management.

Funding

No external funding.

Ethical approval

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

References