Pyoderma gangrenosum presenting with pulmonary manifestations

Introduction

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis often associated with inflammatory bowel disease, inflammatory arthritides, and hematologic abnormalities.¹ Clinically, PG manifests as a rapidly progressing painful lesion with violaceous borders most commonly on the lower extremity. Alternate locations include the arms, trunk, and peristomal skin.¹ Extracutaneous manifestations of PG, while rare, preferentially affect the lungs.² Pulmonary involvement preceding cutaneous manifestations in PG is exceptionally rare, with limited reports in the literature.³ We describe an uncommon case of PG presenting with pulmonary manifestations and present the main clinical and histopathologic features.

Case report

A 53-year-old woman with past medical history of type 2 diabetes mellitus, nonalcoholic steatohepatitis cirrhosis, bipolar disorder, and recurrent granulomatous cavitary lung lesions was hospitalized with severe pain due to a rapidly progressive ulcer on the lower extremity (Fig 1).

Fig 1.

Ulcerated plaque with purple undermined borders on the lateral aspect of the lower extremity consistent with pyoderma gangrenosum.

The patient had a complex pulmonary history, which had started approximately 7 years prior to the development of her ulcer and required several hospitalizations. She initially presented with chest pain, dyspnea, and low-grade hemoptysis related to cavitary lung lesions that only mildly improved with antibiotics. Multiple chest tomographies showed multilobular consolidations with multifocal discoid scarring, ground glass opacities, and cicatricial bronchiectasis at sites of prior consolidations (Fig 2). Tissue cultures from the lung were negative for fungus, bacteria, and acid-fast bacilli. Blastomyces antigen was negative, but she did have a positive histoplasma urine antigen and was subsequently treated with amphotericin B and posaconazole. Despite antifungal therapy, she continued to have persistent dyspnea and hemoptysis. Lung biopsies taken at different hospitalizations revealed a neutrophil–predominant inflammatory process without vasculitis (Fig 3). Serologic workup with antineutrophil cytoplasmic antibodies was negative, as was the subsequent workup for histoplasmosis and other infections. Her cavitary masses improved with steroids, only to recur off therapy. Serum protein electrophoresis revealed 2 separate IgA kappa monoclonal proteins; IgA and immunoglobulin M levels were slightly elevated, and IgG levels were normal. Further workup revealed no evidence of myeloma or other hematologic malignancy.

Fig 2.

Computed tomography chest showing left upper lobe consolidation with ground glass opacities and biapical small centrilobular nodules.

Fig. 3.

Punch biopsy of papulopustule on lower extremity showing neutrophil–predominant dermal inflammation without evidence of vasculitis.

A papulopustule on the leg prompted the initial dermatologic evaluation and was biopsied (Fig 3). The patient returned to the hospital with progressive ulceration at the site of the biopsy. Histopathological findings were not suggestive of vasculitis (Fig 4). While hospitalized for her ulcer, the patient received intravenous steroids and immunoglobulin. She was discharged on oral tacrolimus and prednisone with subsequent improvement in both pulmonary symptoms and gradual healing of the leg ulceration. At the 4-month follow-up, the lower extremity ulcer was almost completely healed.

Fig. 4.

Lung biopsy with neutrophil-predominant inflammation. (Hematoxylin-eosin stain; original magnification: ′100.)

Discussion

Pulmonary involvement in PG that precedes cutaneous lesions is exceptionally uncommon and represents a diagnostic and therapeutic challenge.^2,3 Clinical symptoms of pulmonary involvement in PG are nonspecific, including cough, dyspnea, hemoptysis, and severe respiratory distress.4, 5, 6 Recurrent cavitary lesions may mimic a variety of other conditions, including granulomatosis with polyangiitis, disseminated fungal infection, and malignancy.² Superimposed bacterial and fungal infections can complicate diagnosis and management. There is a reported association between PG with pulmonary involvement and underlying hematologic disease, especially IgA gammopathy. As such, evaluation for underlying malignancy or cell dyscrasias should be performed in suspected cases.²

PG is a diagnosis of exclusion; clinical mimickers such as granulomatosis with polyangiitis, infection, and malignancy must be ruled out first. Chest imaging, lung biopsies, and sputum samples should be obtained in patients presenting with pulmonary symptoms to rule out malignancy and infection. As in the presented case, histopathology can be useful in excluding clinical mimickers in the setting of suspected PG. Histopathological findings of PG include dense sterile neutrophil-predominant infiltrates, which may be seen in both lung and skin biopsies.¹

The development of pathergy-associated PG in response to percutaneous or open lung biopsy can further support diagnosis.² Systemic corticosteroids are the mainstay of treatment for both cutaneous and pulmonary manifestations of PG, with steroid-sparing agents, biologics including tumor necrosis factor-α inhibitors and interleukin-23 inhibitors, Janus kinase inhibitors, and intravenous immunoglobulin being used in patients with recalcitrant disease.⁴ This case underscores the importance of maintaining a high index of suspicion for PG with pulmonary involvement in patients presenting with overlapping cutaneous and pulmonary symptoms not suggestive of another etiology. Prompt dermatological evaluation and histopathological examination can aid in diagnosis and subsequent multidisciplinary management.

Conflicts of interest

Dr Flowers has served as a principal investigator for AbbVie, Acelyrin, AstraZeneca, Clinuvel, Regeneron/Sanofi, and Sun Pharmaceuticals. He has served on advisory boards for Argenx, Bristol-Myers Squibb, and Janssen. The other authors have no conflicts to declare.