Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature

Abstract

Pyoderma gangrenosum (PG) is an uncommon, serious, ulcerating skin disease of uncertain etiology. It manifests as a noninfectious, progressive necrosis of the skin characterized by sterile neutrophilic infiltrates. It seems to be a disorder of the immune system. PG is associated with certain underlying conditions in at least 50% of cases. Therefore, it is important to look carefully for comorbidities in every patient with PG and treat them adequately to improve the prognosis. Here, we demonstrate a 35-year-old man diagnosed with multifocal PG and hemophagocytic lymphohistiocytosis (HLH) with fatal outcome, despite combined, long-term, intensive dermatological and hematological treatment with high doses of steroids, cyclosporin, intravenous immunoglobulins (IVIG), HLH-2004 protocol with intravenously administered etoposide, and anakinra. This case is presented owing to the extremely rare coexistence of PG and HLH and the related diagnostic and therapeutic difficulties. It is also worth underlying that the diagnosis of HLH should perhaps be considered in the presence of a high percentage of double-negative T lymphocytes (DNTs) in flow cytometry, after excluding the diagnosis of lymphoma and leukemia. In this article we have also performed and present the critical literature review of local and systemic options in the management of PG lesions based on a detailed search of the PubMed database.

Keywords: Anakinra; DNTs; Double-negative T lymphocytes; Etoposide; HLH; Hemophagocytic lymphohistiocytosis; Pyoderma gangrenosum.

Fig. 1

Multifocal ulcerations in the course of pyoderma gangrenosum on the lower limbs (a, b) and upper limbs (c, d) on the day of admission. e–h The same lesions 2 weeks after intravenous administration of methylprednisolone followed by prednisone 30 mg and cyclosporin 150 mg twice a day. i–l The same lesions after the second administration of etoposide

Fig. 2

Histopathology of the ulcer edge: subcorneal abscess formation (a); fibrinoid necrosis of the dermal vessel wall (b); pseudoepitheliomatous hyperplasia (c); infiltrate of chronic inflammatory cells and extravasation of red blood cells (d) [hematoxylin and eosin stain, original magnification: a ×40, b–d ×20]

Fig. 3

“Double-negative” CD4⁻/CD8⁻ T lymphocytes* (red), CD4⁺ helper T lymphocytes (green), CD8⁺ cytotoxic T lymphocytes (yellow), CD3⁻/CD16⁺ NK cells (purple). *Full immunophenotypic profile of “double-negative” T lymphocytes: CD3⁺ strong/CD4⁻/CD8⁻/CD2⁺/CD5⁺ dim/CD7⁺/CD56^±/CD57⁻/CD45RA⁻/CD45RO⁻/TCRαβ⁻/TCRγδ⁺

Fig. 4

CD3⁻/CD16⁺ NK cells* (purple), “double-negative” CD4⁻/CD8⁻ T lymphocytes (red), CD8⁺ cytotoxic T lymphocytes (yellow), CD4⁺ helper T lymphocytes (green), B lymphocytes (orange). *Full immunophenotypic profile of NK cells: CD3⁻/CD16⁺/CD56⁺/CD57⁻/CD45RA⁺/CD45RO⁻/CD2⁺/CD5⁻/CD7⁺

Fig. 5

Hemophagocytes in the patient’s bone marrow. Fragments of phagocytosed cells of the erythroid lineage are present within the macrophage cytoplasm

Fig. 6

HLH-2004 diagnostic criteria for hemophagocytic lymphohistiocytosis fulfilled by the patient [17]