Cytophagic Histiocytic Panniculitis Research Articles

Panniculitis: A Cardinal Sign of Autoinflammation.

Panniculitis was first described in the nineteenth century and is characterized by inflammation of the subcutaneous fat. It may be categorized in septal or lobular subtypes, but other histopathological features (e.g., presence of vasculitis, nature of inflammatory infiltrates, characteristics of fat necrosis) are also important for diagnostic purposes. Clinically, panniculitis is characterized by the presence of subcutaneous nodules, and both ulcerative and nonulcerative clinical subtypes have been proposed. In this review, we aimed to describe the occurrence of panniculitis in autoinflammatory disorders (AIDs) and related diseases. Among monogenic AIDs, panniculitis is common in IFN-mediated disorders. Panniculitis is a distinctive feature in proteasome-associated autoinflammatory syndromes (PRAAS), including chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome and Nakajo-Nishimura syndrome. On the other hand, erythema nodosum corresponds to the most common clinical form of panniculitis and is common in polygenic AIDs, such as Behçet's syndrome, inflammatory bowel disease, and sarcoidosis. Cytophagic histiocytic panniculitis, lipoatrophic panniculitis of children, and otulipenia are rare disorders that may also present with inflammation of the subcutaneous fat. Therefore, panniculitis can identify a specific subgroup of patients with AIDs and may potentially be regarded as a cardinal sign of autoinflammation.

Clinicopathological Characteristics and Outcome of Cytophagic Histiocytic Panniculitis: A Single-Center, Retrospective Study.

Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis associated with systemic features characterized by the infiltration of subcutaneous adipose tissue by benign-appearing T lymphocytes and phagocytic histiocytes, mimicking hemophagocytic lymphohistiocytosis (HLH) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). To establish the clinicopathological features and response to treatment of CHP and evaluate the prognosis of patients and guide therapy based on the current state of knowledge. Clinical, laboratory, histopathological, and outcome data of 12 patients with CHP were retrospectively collected between 2009 and 2022. All the patients presented with plaques or nodules, mostly located in the lower extremities (11/12). Fewer cases involved systemic symptoms (9/12) and laboratory abnormalities (6/12), and none were positive for serum Epstein-Barr virus (EBV)-DNA. Histopathological examination revealed mixed septal and lobular inflammatory infiltration of histiocytes and lymphocytes. Large or atypical lymphocytes were rarely present (2/12). In some patients, varying proportions of plasma cells, neutrophils, and eosinophils were observed. The extent of histocytophagy was mild (9/12), moderate (2/12), and severe (1/12). HLH was not observed in any of our cases, none of which were fatal. The uniqueness of our study lies in the presence of neutrophil-rich dermal and subcutaneous infiltrates, associated with connective tissue disorders (CTD) and streptococcal infections. Our study reveals that EBV-negative CHP tends to a better prognosis than previously research, filling the gap in the much-needed details of CHP in the Chinese population. Moreover, CHP may present as a reactive process in combined primary diseases; further studies are required to validate these findings.

Cytophagic Histiocytic Panniculitis with Undetermined Autoimmune Disease: A Rare Case Report

Cytophagic histiocytic panniculitis is a rare disease, associated with either nonmalignant conditions or subcutaneous panniculitis-like T-cell lymphoma (SPTL), and often also associated with hemophagocytic lymphohistiocytosis (HLH). We report the case of a 63-year-old woman who developed a multiple tender, indurated, erythmatous lesions over the abdomen, back, trunk and limbs. Histopathologic findings from skin biopsy specimens revealed significant lobular panniculitis with benign histiocytes showing hemophagocytosis. ANA by IF was positive. Though it is very rare, to confirm diagnosis of CHP by histopathology is very important as CHP and SPLT may span a clinicopathologic spectrum in which there is a natural disease progression from CHP to fatal SPTL.

Intriguing Subcutaneous Nodules – A Panic-Stricken Panniculitis

A 13-year-old boy presented with multiple transient painless swellings over the body for the past 6 months. Lesions would persist for 6–8 weeks and spontaneously resolve leaving behind discolouration and altered skin texture. Clinical examination revealed a single soft, non-tender mobile nodule of 2 × 2 cm over left arm, along with multiple discrete well defined post-inflammatory hypopigmented patches with hyperpigmented scaly papules over the arms, thighs and trunk. Skin biopsy showed lobular panniculitis composed of lymphoid cells, histiocytes and plasma cells with characteristic rimming of fat cells by lymphoid cells suggestive of cytophagic histiocytic panniculitis. Immunohistochemistry showed positive CD3, CD5, CD7 and CD8, negative CD20, CD4, CD56, Ki67 – 75–80%, CD68 highlighting the histiocytes and C30 negative. Positron emission tomography–magnetic resonance imaging showed multiple fluorodeoxyglucose (FDG) avid cutaneous and subcutaneous nodules throughout the body and minimally FDG avid axillary and inguinal lymph nodes. Thereby, a final diagnosis of subcutaneous panniculitis like T-cell lymphoma was concluded. Our patient was started on a tapering dose of oral prednisolone and cyclosporine, following which the lesions significantly improved.

Cytophagic histiocytic panniculitis as a presentation of primary cutaneous gamma/delta T-cell lymphoma

Cytophagic histiocytic panniculitis as a presentation of primary cutaneous gamma/delta T-cell lymphoma

Bilateral ptosis as first presentation of cytophagic histiocytic panniculitis: a case report

BackgroundCytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis that may progress to panniculitis-like T-cell lymphoma. We report a case of CHP that first manifested as bilateral ptosis, which is the first reported case of this presentation.Case presentationA 25-year-old woman without medical history was referred to the neurology department of our hospital for evaluation of bilateral ptosis. Three months previously, she suddenly complained of bilateral ptosis without apparent cause. Simultaneously, non-painful tender subcutaneous nodules and eschar-like skin lesions were observed on her extremities and trunk. A diagnosis of CHP was made based on skin biopsy from the left thigh showing lobular panniculitis, vasculitis, and adiponecrosis, with infiltration of inflammatory cells, including lymphocytes, histiocytes, and phagocytic histiocytes. Her condition continued to worsen with corticosteroid and immunosuppressive agent (thalidomide) treatment. Significant improvement was noticed after three cycles of chemotherapy of THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone).ConclusionsCHP is a rare condition whose clinical presentation may include bilateral ptosis and biopsy is required for diagnosis of CHP.

CGRA16: A CASE OF DEADLY SWELLING

Cytophagic histiocytic panniculitis is a rare form of panniculitis with its most detrimental phenotype thought to be related to subcutaneous panniculitis-like T cell lymphoma, itself an uncommon malignancy. Here, we describe the case of a 27 year old female of Vietnamese heritage who presented with a six week history of severe periorbital oedema and multiple nodules on her extremities. Her investigations revealed anaemia, neutropenia, mildly altered liver function tests, a weakly positive Coomb's test and a titre of ANA with negative ENA, anti-ds DNA and complements. Skin biopsy was consistent with lupus profundus. Diagnosed with a systemic lupus erythematosus and managed with steroids with partial effect, she was closely followed in the Immunology-Rheumatology clinic. She continued to have deranged liver function tests, anaemia, neutropenia, and a rising ferritin level. Further work up also showed an increased ACE level and a positive myositis specific antibody, anti PL-12. Due to her incomplete response to steroids and a worsening ferritin level, investigations to look for evidence of a macrophage activation syndrome returned with an increased soluble CD25 level. Despite the addition of hydroxycholoroquine and mycophenolate, deterioration of her liver function progressed. An emergent hospital admission for acute onset jaundice and general malaise, found her severely anaemic and coagulopathic with active melaena. A review of her initial skin biopsy was done, this time revealing subtle features consistent with a subcutaneous panniculitis-like T cell lymphoma. An emergency bone marrow biopsy confirmed evidence of haemophagocytosis. T cell gene rearrangements on both bone marrow and skin further supported a diagnosis of a peripheral lymphoma. Within her first 48 hours in hospital she required an admission into ICU, multiple endoscopies, a laparotomy and massive blood transfusions. Initially treated with dexamethasone and etoposide, she was started on cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone with remarkable results.

Panniculites cutanées

Panniculitis is an inflammation of the subcutaneous fat. Skin biopsy plays a critical role in the differential diagnosis of panniculitis. The most common approach to diagnosis relies on the differentiation between predominantly septal or lobular panniculitis, followed by the distinction between lesions with and without vasculitis. It is also very important to submit a part of the skin biopsy for microbiological analysis and for T-cell clonal expansion if T-cell lymphoma is suspected. Erythema nodosum, the most frequent septal panniculitis, has many causes and in its typical clinical presentation, does not require skin biopsy. In other panniculitis, diagnosis is based on the integration of the clinical and histological data, which renders a deep cutaneous biopsy necessary. Periarteritis nodosa, a septal panniculitis with vasculitis characterized by subcutaneous nodules and livedo racemosa, can be associated with systemic involvement. Nodular thrombophlebitis needs search for associated coagulopathy, Behçet's disease, periarteritis nodosa or Buerger's disease. Lobular panniculitis are classified according to the nature of cells present in the inflammatory infiltrate. If there is a lymphocytic infiltration, lupus panniculitis is difficult to differentiate from subcutaneous panniculitis-like T-cell lymphoma. If there are histiocytes, it can be a sarcoidosis, a cytophagic histiocytic panniculitis or, in newborn, a subcutaneous fat necrosis. Neutrophilic panniculitis needs careful clinic-pathologic correlation. Treatment of panniculitis can be challenging and is based on the histopathological findings. Frequently, the precise cause of panniculitis cannot be established from the outset, so it is important to follow-up patients and not hesitate to repeat the skin biopsy.

Usefulness of Random Skin Biopsy as a Diagnostic Tool of Intravascular Lymphoma Presenting With Fever of Unknown Origin.

Intravascular B-cell lymphoma (IVBCL) is a rare type of extranodal lymphoma in which the lymphoma proliferates within vascular lumen. One of the most common presenting symptoms is prolonged fever. Although examination of a random skin biopsy from healthy-appearing skin in patients with suspected intravascular lymphoma has been reported to be useful, the sensitivity of this method for diagnosis is still unknown. To evaluate the usefulness of a random skin biopsy in the diagnosis of intravascular lymphoma in the patient presenting with fever of unknown origin. All cases that we performed random skin biopsy were retrospectively reviewed from March 2007 to June 2012 in Ramathibodi Hospital. The incisional biopsy technique was performed in 3 separate locations including 2 specimens from both upper thighs and 1 specimen from the abdomen. Of the 24 cases that were consulted to dermatologist for random skin biopsy, 3 cases (13%) were diagnosed of intravascular lymphoma and all presented with prolong fever, weight loss, and remarkable deterioration in Eastern Cooperative Oncology Group (ECOG) performance status (ECOG score) > 2. Interestingly, 2 cases (8%) were diagnosed with cytophagic histiocytic panniculitis from normal-appearing skin and subsequently investigated, which leads to the diagnosed of T-cell lymphoma. In an elderly patient with fever of unknown origin and/or weight loss with no evident of skin lesion, markedly elevated lactate dehydrogenase, remarkable deterioration in ECOG performance status who suspected IVBCL should be consider to perform incisional random skin biopsy at least 3 specimens from both thighs and abdomen to achieve a high sensitivity. We propose that this technique may serve as an important diagnostic tool to obtain the diagnosis of IVBCL. In summary, 5 of 24 (21%) positive results from random skin biopsy helped diagnoses of lymphoma.

OP0225 Mefv and TNFRSF1A Gene Mutations in Patients with Inflammatory Myopathy with Abundant Macrophages

BackgroundInflammatory myopathy with abundant macrophages (IMAM) is a new clinical condition characterized by diffuse infiltration of macrophages in fascia [1], but the mechanism remains unclear.ObjectivesThe objective of this study was...

Cytophagic histiocytic panniculitis, hemophagocytic lymphohistiocytosis and undetermined autoimmune disorder: reconciling the puzzle

Cytophagic histiocytic panniculitis is a rare disease, associated with either nonmalignant conditions or subcutaneous panniculitis-like T-cell lymphoma, and often also associated with hemophagocytic lymphohistiocytosis (HLH). We report the case of a 11-year-old boy with a history of secondary HLH who, after a local trauma, developed a painful, indurated plaque over the right thigh associated with relapsing HLH. Histopathologic findings from skin biopsy specimens revealed significant lobular panniculitis with benign histiocytes showing hemophagocytosis. High-dose intravenous methylprednisolone and cyclosporine A treatment was highly effective. A genetic study after a new, relapsing episode of HLH revealed an heterozygous missense mutation on STX 11 gene inherited from the mother.

Clonal Cytophagic Histiocytic Panniculitis in Children May Be Cured by Cyclosporine A

Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis in childhood, associated either with nonmalignant conditions or with subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and often also associated with macrophage activation syndrome (MAS). Discriminating between these 2 conditions is therapeutically important because nonmalignant CHP often improves under cyclosporine and prednisone, whereas most cases of SPLT may be best treated with more aggressive therapy. We report the cases of a 6-month-old boy and a 16-month-old girl who, after viral infection, developed multiple infiltrating skin nodules on the limbs and face, associated with MAS. Histopathologic findings for skin biopsy specimens revealed CHP associated with heavily cellular lobular panniculitis. Hemophagocytosis and immunohistochemical staining features were consistent with typical characteristics of in situ MAS in adipose tissue: the lymphocytes were mostly TCD8+ cells with an activated phenotype (human leukocyte antigen (HLA) -DR+) and expressed interferon-γ; CD68+ macrophages expressed tumor necrosis factor-α and interleukin-6. A monoclonal rearrangement of the T-cell receptor γ gene was present in skin tissue but not in peripheral blood or bone marrow lymphocytes. Cyclosporine A treatment resulted in the complete remission of cutaneous and systemic manifestations in both patients for 66 and 29 months, respectively. This report suggests that the diagnosis of a reactive T-cell lymphoproliferation should be the treatment of choice in young children with severe CHP, even if there is a SPTCL-like aspect with an in situ T-cell clonality. It also suggests that CSA is the optimal treatment of this condition and postulates the possible pathologic process underlying this efficacy.

Cytophagic histiocytic panniculitis associated with HBe hemoglobinopathy in a patient with hemophagocytic syndrome

Introduction: Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis which may occur alone or as a part of systemic manifestation of Hemophagocytic syndrome (HPS). It is described as a chronic histiocytic disorder of the subcutaneous adipose tissue with lymphocytic and histiocytic infiltration showing hemophagocytosis. It may also be noted in bone marrow, spleen, lymph nodes and liver. Treatment includes glucocorticoids, cyclosporine and combined chemotherapeutic medications. Observation: A 34 years old lady, presented with multiple nodules over the body since 2 years. Hematological investigations revealed that patient had a rare HbE hemoglobinopathy and was treated for that. Skin biopsy showed CHP and subsequently on hematological and biochemical tests, a diagnosis of HPS was given and patient was referred to a hemato-oncologist. Conclusion: Cytophagic histiocytic panniculitis is a rare and fatal form of panniculitis with multisystem involvement. Awareness of this cutaneous manifestation may help physicians in the early diagnosis of HPS. We report this interesting case of CHP with a brief review of literature. To best of our knowledge this is the first case of Hemophagocytic syndrome associated with HbE hemoglobinopathy.

Comment: Cytophagic histiocytic panniculitis associated with HBe hemoglobinopathy in a patient with hemophagocytic syndrome

comment: Cytophagic histiocytic panniculitis associated with HBe hemoglobinopathy in a patient with hemophagocytic syndrome

Cytophagic histiocytic panniculitis in a 74-year-old man

Cytophagic histiocytic panniculitis is a chronic histiocytic disease of the subcutaneous adipose tissue characterised by lobular panniculitis with histiocytes containing blood cell fragments. It is also associated with marked systemic features such as fever, pancytopenia, hepatosplenomegaly, liver abnormalities and coagulopathy. We report a case of cytophagic histiocytic panniculitis in a 74-year-old man successfully treated using combination therapy with prednisolone and cyclosporine A.

Systemic lupus erythematosus with cytophagic histiocytic panniculitis successfully treated with high-dose glucocorticoids and cyclosporine A

A 37-year-old male with systemic lupus erythematosus (SLE) presented with high fever, subcutaneous indurations, anemia, thrombocytopenia, elevated liver enzymes and hyperferritinemia. Skin biopsy revealed hemophagocytic histiocytes in the adipose tissues. The patient was diagnosed with SLE with cytophagic histiocytic panniculitis (CHP). Treatment with high-dose glucocorticoids and cyclosporine A induced remission of SLE and CHP. CHP is generally a systemic disorder affecting subcutaneous adipose tissues with a high mortality rate. However, based on the present and previously reported cases, we believe that intensive immunosuppression can ameliorate CHP that occurs as a skin manifestation of SLE.

Cytophagic histiocytic panniculitis: is it a macrophage activation syndrome in situ?

Patients A 10-month-old year boy and a 4-month-old-year girl presented with multiple erythematous and indurated noduless on the limbs, and developed high-grade fever and biological features suggestive of MAS several months after the onset of cutaneous disease. Serologic test for EBV was negative and bone marrow examination revealed hemophagocytosis. A homozygous splicing mutation for the UNC13D gene encoding for Munc 13-4 was present in patient 1, but NK cell cytotoxicity and degranulation assays, and expression of Munc 13-4 protein were normal. No mutation was found in Patient 2. Prednisone alone failed to induce a sustained remission which was obtained by adding cyclosporine A.

Cytophagic histiocytic panniculitis with haemophagocytosis in a patient with familial multiple lipomatosis and review of the literature

We report a patient with the extremely rare familial multiple lipomatosis syndrome, who developed the uncommon autoimmune disease cytophagic histiocytic panniculitis, manifested as inflammation of preexisting lipomas. Despite his initial critical condition and unsuccessful treatment with steroids, he responded to cyclosporin and remains well 15 years after diagnosis. In contrast with most previous reports, our patient stays dependent on cyclosporin; repeated attempts of discontinuing or substituting treatment were quickly followed by relapse. Haemophagocytic panniculitis is considered as a T-cell disorder, but its exact pathophysiological mechanism has not been clarified. Differential diagnosis of cytophagic histiocytic panniculitis mainly includes malignant histiocytosis, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus panniculitis (lupus profundus). We discuss the main clinical features, diagnostic challenges and treatment issues of this usually benign, but at times life-threatening autoimmune condition.

Successful treatment of cyclosporine-A-resistant cytophagic histiocytic panniculitis with tacrolimus

A 34-year-old woman with discoid lupus erythematosus and lupus profundus was admitted to our hospital showing signs of a fever, malaise, and abdominal swelling. Diagnosis of cytophagic histiocytic panniculitis (CHP) was made based on lobular panniculitis with a hemophagocytosis. Treatment with high doses of prednisolone combined with cyclosporine A (CsA) was not effective enough. However, after changing CsA to tacrolimus (TAC), CHP improved. Our case demonstrates that TAC may be a novel therapy for CHP.

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.