Subcutaneous panniculitis-like T-cell lymphoma in two unrelated individuals with BENTA disease.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous non-Hodgkin lymphoma involving CD8+ T cells, the genetic underpinnings of which remain incompletely understood. Here we report two unrelated patients with B cell Expansion with NF-κB and T cell Anergy (BENTA) disease and a novel presentation of SPTCL. Patient 1 presented early in life with recurrent infections and B cell lymphocytosis, linked to a novel gain-of-function (GOF) CARD11 mutation (p.Lys238del). He developed SPTCL-like lesions and membranoproliferative glomerulonephritis by age 2, treated successfully with cyclosporine. Patient 2 presented at 13 months with splenomegaly, lymphadenopathy, and SPTCL with evidence of hemophagocytic lymphohistiocytosis. Genetic analysis revealed two in cis germline GOF CARD11 variants (p.Glu121Asp/p.Gly126Ser). Autologous bone marrow transplant resulted in SPTCL remission despite persistent B cell lymphocytosis. These cases illuminate an unusual pathological manifestation for BENTA disease, suggesting that CARD11 GOF mutations can manifest in cutaneous CD4+and CD8+ T cell malignancies.

B Lymphocytes and Adipose Tissue Inflammation.

The immune system plays an important role in obesity-induced adipose tissue inflammation and the resultant metabolic dysfunction, which can lead to hypertension, dyslipidemia, and insulin resistance and their downstream sequelae of type 2 diabetes mellitus and cardiovascular disease. While macrophages are the most abundant immune cell type in adipose tissue, other immune cells are also present, such as B cells, which play important roles in regulating adipose tissue inflammation. This brief review will overview B-cell subsets, describe their localization in various adipose depots and summarize our knowledge about the function of these B-cell subsets in regulating adipose tissue inflammation, obesity-induced metabolic dysfunction and atherosclerosis.

Viral panniculitis in a patient with disseminated opportunistic Enterovirus infection.

Infection-induced panniculitis has been described in association with a broad range of microorganisms. Among those, viral panniculitis represents a minor category, with only a few anecdotal reports in the literature documenting viral infection in the subcutaneous fat. Herein, we report a woman in her 30s with seropositive rheumatoid arthritis on rituximab and prednisone, who presented with a 6-month history of progressive multisystem manifestations, including unintentional weight loss, fever, fatigue, myopathy, pancreatitis, and sensorineural hearing loss. She had indurated plaques on her thighs characterized by predominantly lobular panniculitis with chronic lymphohistiocytic inflammation. Molecular studies performed at the Centers for Disease Control and Prevention identified evidence of Enterovirus group with the highest identity of Coxsackievirus A9. Enterovirus RNA was also detected in the cerebrospinal fluid and muscle. Based on the findings, a diagnosis of disseminated enteroviral infection in the setting of B-cell depletion was rendered. To the best of our knowledge, this represents the first reported case of viral panniculitis with documentation of Coxsackievirus A9 in the skin. Since rituximab may be used for the treatment of autoimmune dermatological diseases, familiarity of the potential occurrence of severe enteroviral infections in the setting of immunosuppressive treatment is important for dermatopathologists.

Panniculitis caused by progesterone injection can be treated by physical therapy.

A method for the treatment of panniculitis caused by progesterone injection is introduced. Sixteen patients achieved good results. This is a 9-year single center retrospective study. Of all the 5633 patients who received progesterone injection, 16 developed panniculitis at the injection site. Pathological examination confirmed the occurrence of panniculitis. The patient received physical therapy. These treatments are determined by the course of the patient. Compared with patients without panniculitis, patients with panniculitis received more than one injection of progesterone. In 16 patients, symptoms and local signs disappeared completely in 15 patients. One patient did not take physical therapy according to the doctor's advice after the treatment improved. However, 1 month later, the patient went to see the doctor again and received the relevant physical therapy, and still achieved good results. Progesterone injection may lead to panniculitis, which is rare but may cause serious consequences. Physical therapy can be effective.

Subcutaneous panniculitis-like T-cell lymphoma in a 14-year-old female homozygous for HAVCR2 mutation.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma preferentially involving subcutis. A link between patients with SPTCL and HAVCR2 mutations has recently been discovered. We present a 14-year-old girl of Chinese heritage who was diagnosed with SPTCL in the context of homozygous HAVCR2 status for c.245A>G p. (Tyr82Cys) and achieved complete remission after treatment with cyclosporin and steroids. Dermatologists should be aware of the diagnostic, management and familial genetic counselling utility of HAVCR2 for investigating and managing patients with SPTCL.

Subcutaneous panniculitis-like T-cell lymphoma: Clinical features, therapeutic approach, and outcome in a case series of 16 patients.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma of mature cytotoxic T cells. Initially, patients with SPTCL were treated with doxorubicin-based polychemotherapy. OBJECTIVE: To analyze clinical, biologic, immunophenotypical, molecular, imaging, treatment, and outcome data reflecting the current state of knowledge. METHODS: A retrospective multicenter study of 16 patients with SPTCL that was diagnosed between 1996 and 2016. RESULTS: The female-to-male ratio was 1.7. The median age at diagnosis was 46.5 years. Patients presented with multiple nodular or plaque-like lesions preferentially affecting the legs and/or trunk. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3+, CD4-, CD8+, CD56-, TIA1 cytotoxic granule associated RNA binding protein 1-positive phenotype and high proliferation rate. SPTCL was associated with autoimmune diseases in 25% of patients, and with the development of hemophagocytic syndrome in 18% of patients. Oral steroids alone or in combination with low-dose methotrexate or cyclosporine A were the most common initial treatment, achieving a complete response in 85% of the treated patients. The median follow-up time was 14 months. The 5-year disease-specific survival rate was 85.7%. LIMITATIONS: This was a retrospective study. CONCLUSIONS: SPTCL has an excellent prognosis. Immunosuppressive agents can be considered for first-line treatment.

[Idiopathic lipoatrophic panniculitis in an adult treated with hydroxychloroquine and adipocyte grafting]. / Panniculite lipoatrophiante idiopathique de l'adulte traitée par hydroxychloroquine et autogreffe de cellules graisseuses.

BACKGROUND: Idiopathic lipoatrophic panniculitis is a rare disease. Various terms are used in the literature to describe similar entities: annular lipoatrophy of the ankles, lipophagic panniculitis and lipoatrophic panniculitis. In any event, it consists of an inflammatory process progressing to necrosis of the fatty tissue. PATIENTS AND METHODS: Herein we report the case of a 37-year-old woman presenting characteristic signs: erythematous, annular, symmetrical, painful, inflammatory lesions of the lower extremities, progressing to areas of atrophy with an indurated inflammatory periphery. Histopathology showed lobular panniculitis composed primarily of lymphocytes and macrophages. The etiological investigations ruled out all other causes of lobular panniculitis. The patient was successfully treated with hydroxychloroquine 400mg/day for 1 year and she subsequently underwent fat grafting on the secondary lesions. DISCUSSION: Our literature review identified 23 reported cases of idiopathic lipoatrophic panniculitis since 2006, including 10 cases of annular ankle lipoatrophy. The most commonly used treatments are corticosteroids, hydroxychloroquine and methotrexate, with good efficacy being seen on the inflammatory phase. This disease seems a good indication for fat grafting to limit aesthetic sequelae. CONCLUSION: Lipoatrophic panniculitis, a rare disease, results in significant aesthetic sequelae which may be limited by early treatment initiation. The benefit-risk ratio of hydroxychloroquine suggests its value as first-line therapy in this pathology. Our case also demonstrates the value of filling of the secondary atrophy by fat grafting after the inflammatory period has ended.

Panniculitis in rheumatology: features of course and outcomes.

AIM: The study of the course and outcomes of panniculitis (PN) in modern rheumatology practice. MATERIALS AND METHODS: We observed 209 patients (pts) (f-185, m-24 in age 17 to 80 years) with the input diagnosis "Erythema nodosum? Undifferentiated panniculitis?" and duration of illness in from 1 week to 25 years, observed in V.A. Nasonova Research Institute of Rheumatology in 2009-2016 years. Along with the general clinical examination, serological, immunological histological and immunohistochemical studies, CT scan of the chest, Doppler (Doppler ultrasound) of the veins of the lower extremities, tuberculin tests and consultations with doctors of other specialties were conducted. Outcomes were assessed after 1-6 years. RESULTS: In 23 pts a secondary character of PN was identified and discovered non-rheumatic underlying disease. Of the remaining 186 cases, the most frequent were pts with erythema nodosum (EN) (n=121), lipodermatosclerosis (LDS) (n=38) and panniculitis of Weber-Christian (PWCh)(n=18). For EN average age (AA) amounted to 38.9±12.6 years, the nodes the nodes were located symmetrically in 93% of cases on all surfaces of the lower and upper extremities (LUE). For LDS AA of the pts was 54±13 years, 68% of the pts noted the increase in the average body mass index (BMI), 79% - showed signs of chronic venous insufficiency (CVI). In 60% of the pts the items were located asymmetrically, localized mainly in the medial (92%) of the surface of the tibia (s). For PWCh AA amounted to 48.4 ± 17.6 years, seals were located on all surfaces of LUE and in 14 cases - on the trunk. CONCLUSION: To clarify the nature of PN it is necessary to conduct a comprehensive survey. The EN is characterized by symmetric defeat of all surfaces LUE more common in people of young age. A distinctive feature of LDS is asymmetrical lesions of the lower extremities in patients with increased BMI and signs of CVI. For PWCh seals are often localized on the trunk.

Pancreatic Panniculitis and Polyarthritis.

PURPOSE OF REVIEW: Polyarthritis can have numerous reasons and may thus constitute a challenge for differential diagnosis. One rare potential reason for sterile polyarthritis is underlying pancreatic disease with systemic hyperlipasemia, most often accompanied by painful skin lesions caused by a subcutaneous inflammatory process known as panniculitis. Systematic evidence on pancreatic panniculitis and polyarthritis is limited, particularly regarding its feature as facultative paraneoplasia with underlying intra- or even extra-pancreatic malignancy. Therefore, we will summarize the current knowledge about this orphan disease including epidemiological, pathophysiological, diagnostic, and treatment aspects in the present review. RECENT FINDINGS: Although direct evidence is lacking, it is highly probable that pancreatic polyarthritis and panniculitis are caused by peripheral lipolytic activity of lipase systemically circulating due to benign (e.g., acute or chronic pancreatitis) or malign (e.g., acinar cell carcinoma (ACC) or adenocarcinoma) pancreatic disease. In the latter case, pancreatic polyarthritis and panniculitis are associated with poor outcome. Pancreatic polyarthritis and panniculitis should always be included into diagnostic considerations, and once suspected, a thorough work-up to identify the underlying disease has to be performed.

[Obesity and autoimmunity : Adipose tissue as an immune organ?] / Adipositas und Autoimmunität : Fettgewebe als Immunorgan?

Adipose tissue possesses crucial immunological features in the development of comorbidities of obesity. Complex interactions between the metabolic system and cells of the immune system are the cause but are not fully understood. Autoimmune diseases might therefore be influenced by obesity. Epidemiological studies provide evidence of only a modest association between obesity and the development of rheumatoid arthritis and psoriatic arthritis. In obesity the course of inflammatory rheumatic diseases is aggravated, as subjectively measured by activity parameters; however, laboratory parameters show no differences and radiographic examinations reveal less bone destruction in obesity. Furthermore, there are indications for a poorer response to treatment especially with infliximab in patients with an increased body mass index (BMI). Weight loss has a positive effect on the course of joint diseases. Due to deficits in the currently available studies there is insufficient evidence to recommend individualization of treatment decisions based on the BMI.

[A rare cause of severe panniculitis]. / Eine seltene Ursache einer schweren Pannikulitis.

A 58-year-old patient presented with a severe, episodic panniculitis of the upper legs. Necrosis of the fatty tissue and a suspected superinfection led to amputation of one leg. The panniculitis was caused by a hereditary deficiency of alpha-1 antitrypsin (AAT) due to a ZZ mutation of the AAT gene. Neutrophilic panniculitis is found in 0.1% of patients with the ZZ mutation and therefore is the rarest clinical manifestation of AAT deficiency. With the exception of mild COPD, the patient had no other typical clinical symptoms of AAT deficiency. Treatment with colchicum reduced the frequency and severity of the flares.

[Subcutaneous panniculitis-like T-cell lymphoma : Two case reports]. / Subkutanes pannikulitisartiges T-Zell-Lymphom : Zwei Kasuistiken.

Histopathology, immunohistochemical, and molecular genetic findings revealed the diagnosis of subcutaneous panniculitis-like T-cell-lymphoma in two patients, aged 44 and 70 years. The clinical morphology of the lymphoma manifestations showed varied significantly. One patient presented with a singular erythematous nodule in the chin region. The other patient suffered from extended plate-like resistances and atrophy of the face, upper arms and left breast. Hemophagocytic syndrome was not present in either patient. Prognosis of subcutaneous panniculitis-like T-cell lymphoma without associated hemophagocytic syndrome is reported to be favorable. Radiotherapy of the singular lesion on the chin and systemic corticosteroids of the extended plaques induced complete remission in both patients.

[Annular lipoatrophy of the ankles treated by fat grafting: Case report and review of the literature]. / Lipoatrophie annulaire des chevilles traitée par autogreffe de tissu graisseux : à propos d'un cas et revue de la littérature.

INTRODUCTION: Annular lipoatrophy of the ankles is a rare disease. Eleven cases are described in the literature. CASE REPORT: We report the case of a 10-year-old girl having an annular lipoatrophy of the ankles. The clinical history begins with the appearance of inflammatory infiltrated nodules at the two legs, which have evolved in a few months to a circumferential lipoatrophy of the ankles. Laboratory studies showed a very high antistreptolysin O titer, concluding streptococcal origin of this hypodermitis. After two years of stable lesions, the patient received two sessions of fat injection. RESULT/DISCUSSION: A satisfactory outcome of the adipocyte graft was observed with reconstitution of shapely legs, stable over time. Eleven cases described in the literature are found. It is a pediatric pathology seen predominantly in female children. The evolution towards lipoatrophy is systematic with or without treatment initiated at the inflammatory phase. We first discuss the management of aesthetic sequelae of this disease. CONCLUSION: Fat grafting appears to be a good indication for the treatment of the cosmetic sequelae seen in annular lipoatrophy of the ankles.

Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease.

BACKGROUND & AIMS: Patients with alcoholic liver disease (ALD) display inflammation of the subcutaneous adipose tissue (SAT) which correlates with liver lesions. We examined macrophage markers and polarization in the SAT of alcoholic patients and adipokine expression according to liver inflammation; we studied the consequences of alcohol withdrawal. PATIENTS AND METHODS: Forty-seven patients with ALD were prospectively included. SAT and blood samples were collected at inclusion and after 1 week of alcohol withdrawal. Pro-inflammatory cytokines/chemokines, inflammasome components and products, adipokine expression levels, macrophage markers and polarization in liver and SAT samples were assessed by RT-PCR arrays. RESULTS: mRNA expression level of chemokines (IL8, semaphorin 7A) correlated with hepatic steatosis in both liver and SAT. Liver expression of inflammasome components (IL1ß, IL18, caspase-1) and SAT IL6 and CCL2 correlated with liver damage. In patients with mild ALD, 1 week of alcohol withdrawal was sufficient to decrease expression level of total macrophage markers in the adipose tissue, to orient adipose tissue macrophages (ATM) towards an anti-inflammatory M2 phenotype and to decrease the mRNA expression of cytokines/chemokines (IL18, CCL2, osteopontin, semaphorin 7A). In patients with severe ALD, 1 week of abstinence was also associated with an increase in CCL18 expression. CONCLUSIONS: In alcoholic patients, upregulation of chemotactic factors in the liver and SAT is an early event that begins as early as the steatosis stage. The inflammasome pathway is upregulated in the liver of patients with ALD. One week of alcohol withdrawal alleviates macrophage infiltration in SAT and orients ATM towards a M2 anti-inflammatory phenotype; this implicates alcohol in adipose tissue inflammation (ClinicalTrials.gov NCT00388323).

Extracorporeal shock wave therapy for injection site panniculitis in multiple sclerosis patients.

BACKGROUND: Painful cutaneous injection site reactions may hamper treatment with interferon ß (IFN-ß) and glatiramer acetate (GA) in multiple sclerosis (MS) patients. OBJECTIVE: To maintain therapy adherence, efficient therapeutic modalities for these subcutaneous inflammatory lesions are urgently needed. We tested the application of local extracorporeal shock wave therapy (ESWT). METHODS: We applied 5 sessions of ESWT to 8 patients suffering from MS who had developed painful panniculitis at the injection sites of either IFN-ß or GA. Clinical outcomes, i.e. pain reduction and regression of induration, were assessed 3 and 6 months after completion of the ESWT using a visual analogue score. RESULTS: All patients showed both significant pain reduction and reduction of the skin induration in the treated lesions, while in untreated control lesions there was no improvement. CONCLUSION: ESWT proved to be a non-invasive, safe and efficient physical treatment modality for injection-induced painful cutaneous side effects of disease-modifying drugs in MS.

[Pancreatic panniculitis with multiple osteolytic lesions]. / Pankreatische Pannikulitis mit multiplen osteolytischen Läsionen.

A 62-year-old man with a history of chronic alcohol abuse presented with severe pancreatic panniculitis associated with an acute exacerbation of chronic pancreatitis.

Severe postoperative wound healing disturbance in a patient with alpha-1-antitrypsin deficiency: the impact of augmentation therapy.

Wound healing disturbance is a common complication following surgery, but the underlying cause sometimes remains elusive. A 50-year-old Caucasian male developed an initially misunderstood severe wound healing disturbance following colon and abdominal wall surgery. An untreated alpha-1-antitrypsin (AAT) deficiency in the patient's medical history, known since 20 years and clinically apparent as a mild to moderate chronic obstructive pulmonary disease, was eventually found to be at its origin. Further clinical work-up showed AAT serum levels below 30% of the lower reference value; phenotype testing showed a ZZ phenotype and a biopsy taken from the wound area showed the characteristic, disease-related histological pattern of necrotising panniculitits. Augmentation therapy with plasma AAT was initiated and within a few weeks, rapid and adequate would healing was observed. AAT deficiency is an uncommon but clinically significant, possible cause of wound healing disturbances. An augmentation therapy ought to be considered in affected patients during the perioperative period.

[Panniculitis of the thigh and lung emphysema in a 54-year-old patient]. / Pannikulitis des Oberschenkels und Lungenemphysem bei einem 54-jährigen Patienten.

This article reports a case of febrile, symmetrical and painful soft tissue swelling on both thighs in a 54-year-old otherwise healthy male patient. Histologically, necrotizing panniculitis of subcutaneous adipose tissue was described as a marker manifestation of a previously unknown alpha-1-antitrypsin (A1AT) deficiency with pulmonary emphysema and low plasma A1AT levels. The PiZZ homozygous form of A1AT could be diagnosed by gene sequencing. Complete remission of panniculitis could be achieved by A1AT replacement therapy.