Cytophagic histiocytic panniculitis: report of two cases.

Cytophagic histiocytic panniculitis (CHP) was first described in 1980 by Winkelmann as a chronic histiocytic disease of the subcutaneous adipose tissue, which is characterized clinically by tender erythematous nodules, recurrent high fever, malaise, jaundice, organomegaly, serosal effusions, pancytopenia, hepatic dysfunction, and coagulatory abnormalities. CHP may occur either isolated or as part of cutaneous manifestations of hemophagocytic syndrome. Here, we report two different presentations of CHP.

Introduction

Winkelmann first described CHP as a histiocytic disorder with multi-system involvement. It is now known that CHP can present in a clinical spectrum varying from isolated skin lesions to severe systemic involvement. [12] We present two cases representing different clinical presentations of CHP.

Case Reports

Case 1

Our first case was a 36-year-old woman with a history of multiple, painful, erythematous and indurated skin lesions over the limbs and trunk of 1-month duration, along with fever and general malaise. At the time of admission, she was afebrile. Apart from axillary lymphadenopathy, the result of general and systemic examination was within normal limits. Cutaneous examination revealed multiple erythematous tender indurated subcutaneous nodules over the trunk and limbs [Figure 1]. Significant laboratory investigations findings included anemia (Hb - 8.84 g/dl) and mild elevation in liver transaminase levels. Activated partial thromboplastin time (APTT) was deranged (39.9/30.33 sec), but the fibrinogen activity was found to be normal. Also, increased levels of lactate dehydrogenase (904 U/L), serum ferritin (1,000 ng/ml), C-reactive protein (41 mg/ml) and erythrocyte sedimentation rate (ESR; 30 mm/hr) were noted. Autoantibody profile was negative. Although her angiotensin converting enzyme (ACE) level was on the higher side (66.6U/L), calcium levels were within normal limits. The Alpha-1 anti-trypsin level was normal. Results of preoperative serology were negative, which included serology for HIV 1 and HIV 2, hepatitis B and C virus.

Figure 1

Indurated lesions on the right arm

Case 2

Our second case was a 33-year-old woman who presented with a history of high-grade intermittent fever of 8-month duration, associated with malaise and loss of weight since last 6 months. She had noticed painful erythematous, swelling over the abdomen, back and limbs, along with edema of extremities for last 3 months. At the time of admission, her vital signs were stable. Systemic examinations showed minimal ascites and hepatomegaly. Cutaneous examination revealed multiple, indurated, erythematous, subcutaneous swellings, few of which showed ulcerations, necrosis and superficial ecchymosis over the abdomen, back and extremities [Figure 2]. No other significant skin or mucosal lesions were noted. At the time of admission, investigations showed significant leukopenia and thrombocytopenia. Liver function tests were deranged, with highly elevated liver enzymes (SGOT - 691 IU/L, SGPT - 683.0 IU/L, and ALP - 303 IU/L). Prothrombin time (22.6/13.1/1.72 sec) as well as APTT (49.8 /30 sec) were deranged, with low fibrinogen activity (99.5 mg/dl, normal range: 200-400 mg/dl). Auto-antibody profile was negative. Her LDH levels were high (2,856 U/L). Results of preoperative serology were negative, which included serology for HIV 1 and HIV 2, hepatitis B and C virus.

Figure 2

Indurated nodules with superficial ecchymosis and necrosis

Skin biopsy of both patients showed septal and lobular inflammation of subcutaneous tissue, with focal hemorrhagic necrosis. In some areas, macrophages showed phagocytosis of RBCs, lymphocytes and neutrophils (bean bag cells) [Figure 3]. No cellular atypia was noted. Peripheral blood smear as well as bone marrow studies showed no atypia.

Figure 3

Bean bag cells H and E stain; ×100

Based on the above findings, both patients were diagnosed with CHP, with the second patient having hemophagocytic syndrome (HPS) as well. The first patient was started on systemic steroids (prednisolone 40 mg/day), which were continued for 3 months, and as there was recurrence of symptoms with fever, she was added on cyclosporine at a dose of 100 mg/day. She is on regular follow-up for the last two months, with no recurrence of skin lesions.

The second patient was started on dexamethasone 16 mg along with cyclosporine 100 mg daily. After this, her skin lesions subsided and coagulation parameters and liver function test results returned to normal over a period of 1 month. The patient had intermittent relapses and the dosage of steroids and cyclosporine was adjusted accordingly. She is currently on regular follow-up, and her coagulation profile, liver function tests and counts are within the normal ranges.

Discussion

The diagnosis of CHP relies mainly on the histopathology, which characteristically shows prominent chronic inflammation of the fat tissue infiltrated mainly by the benign appearing T lymphocytes and the occasional phagocytic histiocytes (bean bag cells).[3] Erythrophagocytosis and cytophagocytosis by benign-appearing histiocytes can also be observed in internal organs, particularly the lymph nodes, spleen, liver, and bone marrow.[4]

Although the exact etiology of HPS is still not clear, numerous diseases have been shown to be associated with HPS, which include hematological diseases such as acute leukemia, malignant lymphoma, infections (viral, bacterial, fungal, and parasitic). Human immunodeficiency virus (HIV) infections are one of the infectious etiologies considered to be associated with HPS, and it is recommended that all suspected patients with HPS be screened for HIV. Systemic autoimmune diseases, such as SLE and adult-onset Still's disease, have also been reported to be associated with HPS.[235-7]

The clinical manifestations can be attributed to increased secretion of cytokines from activated T/NK cells and macrophages, which, in turn, suppress the hematopoiesis by causing prominent hemophagocytosis in the bone marrow, spleen, liver, and lymph nodes. In addition, cytokine-activated monocytes and vascular endothelial cells may produce procoagulant substance (tissue factor), plasminogen activator inhibitor-1, von Willebrand factor as well as adherent molecules in the cell surface.[8-11] While some patients with CHP suffer from relatively indolent variants of the disease, many others die as a result of massive visceral hemorrhage or organ system failure.[3]

CHP is generally treated with systemic corticosteroids. Methyl-prednisolone pulse therapy has been advocated as a treatment option. Alternate immunosuppressive therapy, such as cyclosporine, maybe used as a first-line treatment.[12] Ito et al, reported a case with CHP treated successfully with a combination of cytotoxic drugs [CHOP - cyclophosphamide, doxorubicin, vincristine and prednisolone] and cyclosporine.[13] In severe relapse cases, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation can be considered an alternative treatment option.[14]

Summing up, CHP is a rare and often fatal form of panniculitis with multisystem involvement. However, it can also present in a benign form involving only the subcutaneous tissue, thus having a broad clinical spectrum.