Bilateral hemorrhage of lower legs evolving into gangrene in a young woman with systemic symptoms

A 19-year-old woman was referred to the wound clinic of our dermatology department showing extensive gangrenous skin next to ulcerated and partially scarred tissue on both lower legs (Figure 1a). Nine months earlier, she had suddenly developed persistent fever and was admitted to the intensive care unit (ICU) for her poor general condition, hypotension, strong muscle pain, and sore throat. At that time, she did not report any pre-existing medical conditions and was not taking medication. However, she had suffered from mild arthralgias of her fingers and salmon-colored exanthemas over the past years. After admission to the ICU she developed extensive hemorrhage on both lower legs (Figure 1b). Diagnostic findings included peripheral blood pancytopenia (erythrocytes: 2.07/pl, leukocytes: 1.2/nl, thrombocytes: 26/nl), splenomegaly, hepatomegaly, lymphadenopathy, and hyperferritinemia (39,700 ng/ml). In addition, neutropenia (0.92/nl), elevated CRP (214.3 ng/l), elevated transaminases (GOT: 83 U/l) and hypertriglyceridemia (424 mg/dl) were observed. A bone marrow biopsy revealed a hypocellularity and hemophagocytosis by CD68 positive cells (Figure 2a, b). Further diagnostic investigations ruled out underlying bacterial (blood cultures), virologic (ELISA, PCR from peripheral blood) or paraneoplastic conditions (CT-cans, tumor serum markers). Moreover, autoimmune laboratory workup was unremarkable for markers of rheumatoid disease or systemic lupus erythematosus (RA, anti-CCP, ANCA, ANA, anti-ds-DNA, C3, C4). Your diagnosis? … Diagnosis: Purpura fulminans in adult-onset Still's disease with secondary hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC) Due to severe clinical symptoms the classic treatment of acquired hemophagocytic syndrome with dexamethasone, ciclosporin, and intermittent administration of immunoglobulins was initiated on the ICU. As disseminated intravascular coagulopathy (DIC) occurred despite anticoagulation, treatment of the hemophagocytic syndrome was extended by etoposide and anticoagulation was escalated (enoxaparin 30 mg BID). The symptom-complex of fever, arthralgias, and salmon-colored exanthema led to the diagnosis of Still's disease as the cause of hemophagocytic syndrome, and etoposide was replaced by anakinra with a daily subcutaneous dose of 100 mg. While the patient's general condition improved significantly, the extensive hemorrhages of her lower legs evolved into gangrene. At the first presentation to our dermatological wound clinic (Figure 1a) we initiated a surgical debridement under local anesthesia and maggot debridement therapy (MDT) (Figure 3a–c). Moreover, home wound care and compression therapy by a nursing service was started to alleviate lymphoedema. Our patient is currently asymptomatic and stable while under treatment with 100 mg cyclosporine and 5 mg prednisolone daily (anakinra was discontinued). At the latest consultation all wounds were closed (Figure 3d). In our patient, purpura fulminans and extensive gangrene were caused by adult-onset Still's disease with secondary hemophagocytic syndrome and DIC. The diagnosis of Still's disease is facilitated by using diagnostic criteria established by Yamaguchi et al.1, 2 Five criteria, including at least two major criteria (prolonged episodes of fever > 39°C, arthralgias or arthritis, typical rash, and elevated leucocyte count with neutrophilia) and three minor criteria (sore throat, hepatomegaly or splenomegaly, lymphadenopathy, abnormal aminotransferases and negative rheumatoid factor and anti-nuclear antibody) must be met for the diagnosis of Still's disease. Based on the medical findings in our patient, all major and minor criteria were met. Purpura fulminans, accompanied by intravascular coagulopathy and microemboli, is clinically characterized by sharply demarcated erythematous macules that rapidly transform into large black-purplish skin areas. Some lesions may show thin erythematous borders or blisters.3 Purpura fulminans is categorized into neonatal, idiopathic and acquired forms, the latter being caused by severe septic infections or hemophagocytic syndrome.4 Treatment of the underlying disease in combination with anticoagulation needs to be initiated quickly, to prevent progression and ultimately multiple organ failure.4 In neonatal forms, that are associated with a hereditary deficiency of anticoagulant proteins C and S, substitution of deficient factors is crucial.3 After a cautious risk-benefit assessment, considering that DIC has a risk of both bleeding and clotting, our patient received a low-dose anticoagulation with enoxaparin (0,5 mg/kg bodyweight BID). Once skin necrosis has already occurred, as in the presented case, extensive ulcerations may arise and surgical debridement, fasciotomy, amputation, and plastic reconstruction may become necessary.3 While early removal of gangrenous skin is the initial treatment of choice, split skin transplantation and measures of conservative wound therapy (e.g. hydrocolloid dressings, vacuum-assisted closure) may accelerate wound healing. Our patient declined split skin transplantation as she feared further scarring at the donor site. Now, 2.5 years after onset of purpura fulminans, all wounds in our patient are completely healed. Our presented case highlights the potentially life-threatening course of purpura fulminans and its association with acquired hemophagocytic syndrome in Still's disease as one rare underlying condition. In our patient, early diagnosis and initiation of the treatment helped to prevent serious consequences such as amputation or multiple organ failure. None.