Ruxolitinib Monotherapy for a Child With HAVCR2 Gene Mutation Associated Subcutaneous Panniculitis-like T-cell Lymphoma: A Case Report.

BACKGROUND: The occurrence of hemophagocytic lymphohistiocytosis (HLH) in patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) may be due to HAVCR2 gene mutation, leading to T-cell immunoglobulin and mucin domain-containing molecule 3 deficiency, T-cell and macrophage activation, and proinflammatory cytokine production. OBSERVATION: We report a patient with SPTCL and HLH for whom ruxolitinib, used as a novel treatment, showed notable therapeutic effects. CONCLUSIONS: Remission of both HAVCR2 mutation-induced high inflammatory characteristics and significant symptoms post-ruxolitinib administration suggested that patients with SPTCL and HLH may not represent typical lymphoma cases. Ruxolitinib, with its relatively low toxic side effects, can provide favorable outcomes.

Efficacy of ruxolitinib for HAVCR2 mutation-associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children.

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.

Centrifugal lipodystrophy on a spectrum with lupus erythematosus panniculitis in children and efficacy and safety of hydroxychloroquine: A clinicopathological study.

This study aimed to investigate the relationship between centrifugal lipodystrophy (CLD) and lupus erythematosus panniculitis (LEP), and the efficacy and safety of hydroxychloroquine (HCQ) for treating CLD in children. A total of 29 cases clinically diagnosed as CLD (n = 24) and CLD/LEP overlap (n = 5) were enrolled and all were confirmed by skin biopsies of CLD and LEP. The clinicopathological findings, clinical outcomes, and prognosis with the treatment of HCQ between CLD and LEP were compared. All 29 cases (male: female = 1:1.6; median age at onset: 3 years) had cutaneous lesions of centrifugally expanding lipoatrophy, of which five cases overlapped with LEP lesions presented as erythematous indurated plaque (n = 2), subcutaneous nodules (n = 2) and alopecia along Blaschko's lines (n = 1). Antinuclear antibodies were found in six (25.0%) CLD and two (40.0%) overlapped patients (p = 0.597). Histopathologically, of the 24 cases of CLD, 14 (58.5%) exhibited subcutis loss or mild lobular inflammation. Ten (41.7%) cases displayed lobular panniculitis with moderate to dense lymphohistiocytic infiltrate and plasma cells, similar to the five cases of overlap. Small clusters of CD123 positive plasmacytoid dendritic cells were found in 62.5% (5/8) of CLD and 66.7% (2/3) of overlap cases (p > 0.99). HCQ (5 mg/kg/d) treatment showed improvement in 91.3% (21/23) of CLD and all overlap cases, including four cases unresponsive to previous oral glucocorticosteroid treatment. Our findings suggested that CLD and LEP represent a spectrum within the same disease. HCQ (5 mg/kg/d) was effective and safe for treating CLD (age >1.5 years), and early treatment and a regular long-term follow-up are essential.

Management of Peripheral T-Cell Lymphoma in Children and Adolescents Including STAT 3 Mutation Hyper-IgE Syndrome: One Size Does Not Fit All.

Peripheral T-cell lymphoma (PTCL) is a rare form of lymphoma in children with limited published data on treatment and lack of a uniformly accepted treatment algorithm. We retrospectively analyzed the data in children up to 18 years of age diagnosed to have PTCL from January 2016 to June 2020. The study included six children with a median age of 10 years, the youngest being a 7-month-old girl. According to the WHO-PTCL classification, three had PTCL-not otherwise specified (NOS), 2 had hepatosplenic TCL, and 1 had subcutaneous panniculitis-like TCL. All children had presented with advanced disease, 4 in St. Jude stage IV, 2 in St. Jude stage III. Three children received CHOEP chemotherapy including cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide, while 1 child received CHOP. Two children received induction as per acute lymphoblastic leukemia followed by Bendamustine. Two patients succumbed to progressive disease, the infant with PTCL-NOS and 1 child with hepatosplenic TCL. Three children were in remission (median follow up of 44 mo). One child with PTCL-NOS Stage IV had an underlying STAT3 mutated hyperimmunoglobulin E syndrome and was in remission 12 months post a matched unrelated donor hematopoietic stem cell transplantation. He had grade 4 skin graft versus host disease and required extracorporeal photopheresis and ibrutinib, to which he had responded. CHOEP chemotherapy is well-tolerated and subcutaneous panniculitis-like TCL has the best prognosis thus far.

Subcutaneous panniculitis-like T-cell lymphoma: brief review and report of successful treatment with mycophenolate mofetil.

Subcutaneous panniculitis-like T-cell lymphoma is a rare, indolent cutaneous cytotoxic alpha-beta T-cell lymphoma, where no specific therapy regimen is defined. We present a case with a diagnostically challenging association with anti-double stranded DNA and provides one of the first reports of a successful treatment with mycophenolate mofetil and glucocorticosteroids.

Pediatric Subcutaneous Panniculitis-like T-cell Lymphoma of the Orbit.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and distinct subtype of peripheral T-cell lymphoma, representing <1% of all non-Hodgkin lymphomas. SPTCL usually arises in the fourth decade of life with multifocal involvement of the limbs and trunk. Orbital disease is uncommon. We present the youngest known case of orbital SPTCL in a 3-year-old child, where the diagnosis was initially confounded by a lower eyelid mass masquerading as preseptal cellulitis. MRI revealed a poorly defined anterior orbital mass. Immunophenotyping and histological analysis of an orbital biopsy specimen confirmed SPTCL, which was managed by the pediatric oncology team with multiagent chemotherapy. This case is unique due to the young age of presentation and primary orbital involvement. Nonresolving or atypical periorbital cellulitis needs to be investigated, as malignancy can mimic such conditions.

Lucio phenomenon with concomitant necrotizing fasciitis and acute kidney injury.

Lucio phenomenon is a rare vasculopathy that can occur in patients with Hansen disease, particularly diffuse lepromatous leprosy. It is characterized by retiform purpura and necrotic ulcerations, most commonly affecting the extremities. Diagnosing Lucio phenomenon can be challenging, especially when secondary bacterial infections occur. We report a patient with Lucio phenomenon who presented with acute necrotizing fasciitis of his left upper extremity and a 10-year history of chronic ulcerations. Shortly following admission, he also developed acute kidney injury. The necrotizing fasciitis was treated with prompt surgical debridement and intravenous antibiotics. Biopsy and PCR of a right upper extremity ulcer confirmed the presence of Mycobacterium lepromatosis. Multidrug therapy and prednisone were used to treat the Lucio phenomenon. After initiating treatment, no new lesions developed, kidney function improved, and the patient underwent successful skin graft of his left upper extremity. Although corticosteroid use is controversial, our patient's marked response to multidrug therapy with prednisone highlights the importance of this regimen in severe presentations of Lucio phenomenon. To the best of our knowledge, only two other cases of Lucio phenomenon confirmed to be caused by M. lepromatosis have been reported in living patients (rather than retrospectively identified post-mortem), underscoring the importance of the presented clinical course and treatment regimen.

Subcutaneous panniculitis-like T cell lymphoma presented as erythema nodosum: A case report.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is an extremely rare subtype of primary cutaneous T cell lymphomas mimicking panniculitis. Clinically, patients are usually presented with subcutaneous nodules, which usually leads to initial misdiagnosis as a benign cutaneous condition. Here, we report a 40-year-old female who presented with subcutaneous erythematous nodules on her extremities with fever. On the basis of the clinical presentations, histopathological features and immunohistochemical findings, a diagnosis of SPTCL was made. The patient was treated with the injection of recombinant human interferon α-1b (30 µg) every other day for 3 months. The lesions gradually regressed. No new erythema nodules reappeared during the 10-month follow-up.

Subcutaneous Panniculitis-like T-Cell Lymphoma With Hemophagocytic Lymphohistiocytosis Syndrome in Children and Its Essential Role of HAVCR2 Gene Mutation Analysis.

BACKGROUND: We identified 3 adolescents with alpha-beta subtype subcutaneous panniculitis-like T-cell lymphoma. CASE PRESENTATION: Three patients presented with prolonged fever, abnormal skin lesions, and cytopenia described in the context. All had the same disease entity, which showed the prolonged duration of B systemic symptoms till diagnosis, difficulty to distinguish from autoimmune diseases, presence of hemophagocytic lymphohistiocytosis syndrome, good response, and remained on long-term remission with nonchemotherapy treatment, which included oral corticosteroid and cyclosporin. CONCLUSIONS: Although diagnosis can only be "highly suspected" with pathologic review, some cases may need multiple serial skin biopsy to clarify diagnosis because of the discrete distribution of specific histology. T-cell receptor gene rearrangement, which demonstrates a monoclonal pattern of alpha and beta chain gene, is the essential requirement for specific diagnosis. The role of molecular analysis by identification of germline hepatitis A virus cellular receptor 2 (HAVCR2) gene mutation can be much valuable in classifying susceptible patients.

Erythema induratum of Bazin in a 10-year-old boy.

Erythema induratum of Bazin (EIB) is a form of tuberculid resulting from hypersensitivity to tuberculosis antigen. EIB occurs most commonly in middle-aged women and is not typically seen in children. Here, we present a rare case of EIB, presenting as a chronic nodular panniculitis, in a 10-year-old Korean boy.

Pyogranulomatous panniculitis in a domestic cat associated with Pseudomonas luteola infection.

Pseudomonas luteola, a pathogen causing disease in humans, has in animals been reported only in rainbow trout and ferrets. This case report describes pyogranulomatous panniculitis in a cat associated with P. luteola infection. Organisms were seen histologically and identified with PCR and sequencing. Lesions resolved after treatment with marbofloxacin.

Pseudomonas luteola, un pathogène de l'homme, a été décrit chez l'animal seulement chez le furet et la truite arc en ciel. Ce cas clinique décrit une panniculite pyogranulomateuse chez un chat associée à une infection à P. luteola. Les organismes ont été vus à l'examen histopathologique et identifiés par PCR et séquençage. Les lésions se sont résolues après un traitement à la marbofloxacine.

Pseudomonas luteola, un patógeno que causa una enfermedad en los seres humanos, se ha reportado en animales solo en truchas arco iris y hurones. Este caso clínico describe una paniculitis piogranulomatosa en un gato asociada con una infección por P. luteola. Los organismos se observaron histológicamente y se identificaron mediante PCR y secuenciación. Las lesiones se resolvieron después del tratamiento con marbofloxacina.

Pseudomonas luteola é um patógeno causador de doença em humanos e, em animais, há relatos de sua ocorrência apenas em furões e trutas arco-íris. Este relato descreve um caso de paniculite piogranulomatosa em um gato associada à infecção por P. luteola. Os microrganismos foram observados histologicamente e identificados por PCR e sequenciamento. As lesões foram resolvidas após tratamento com marbofloxacino.

Oxytocin reduces adipose tissue inflammation in obese mice.

BACKGROUND: Obesity and adipose tissue expansion is characterized by a chronic state of systemic inflammation that contributes to disease. The neuropeptide, oxytocin, working through its receptor has been shown to attenuate inflammation in sepsis, wound healing, and cardiovascular disease. The current study examined the effects of chronic oxytocin infusions on adipose tissue inflammation in a murine model of obesity, the leptin receptor-deficient (db/db) mouse. METHODS: The effect of obesity on oxytocin receptor protein and mRNA expression in adipose tissue was evaluated by Western blotting and real-time polymerase chain reaction. Mice were implanted with osmotic minipumps filled with oxytocin or vehicle for 8 weeks. At study endpoint adipose tissue inflammation was assessed by measurement of cytokine and adipokine mRNA tissue levels, adipocyte size and macrophage infiltration via histopathology, and plasma levels of adiponectin and serum amyloid A as markers of systemic inflammation. RESULTS: The expression of adipose tissue oxytocin receptor was increased in obese db/db mice compared to lean controls. In adipose tissue oxytocin infusion reduced adipocyte size, macrophage infiltration, IL-6 and TNFα mRNA expression, and increased the expression of the anti-inflammatory adipokine, adiponectin. In plasma, oxytocin infusion reduced the level of serum amyloid A, a marker of systemic inflammation, and increased circulating adiponectin. CONCLUSIONS: In an animal model of obesity and diabetes chronic oxytocin treatment led to a reduction in visceral adipose tissue inflammation and plasma markers of systemic inflammation, which may play a role in disease progression.

Mycobacterium porcinum causing panniculitis in the cat.

A 4-year-old domestic shorthair cat was presented with a 7-month history of nodules and draining fistulous tracts of the ventral abdomen. Histopathological examination of affected tissue revealed acid-fast bacilli stained by the Ziehl-Neelsen procedure. Deep tissue culture confirmed infection with a rapidly growing mycobacterium, and gene sequencing characterized the organism as Mycobacterium porcinum. Treatment with pradofloxacin and doxycycline resulted in clinical resolution of the lesions. On continued antibiotic therapy 7 months later, there was no local recurrence nor were there clinical signs associated with distant spread of the infection. This is the first clinical description of a feline infection with this organism. Key clinical message: This is the first clinical description of mycobacterial panniculitis in a cat due to genetically characterized Mycobacterium porcinum. This case report highlights a disease entity that can present a diagnostic and therapeutic challenge to clinicians.

Panniculite chez un chat causée par Mycobacterium porcinum . Un chat domestique à poil court âgé de 4 ans fut présenté avec une histoire d'une durée de 7 mois de nodules et de trajets fistulaires drainants à l'abdomen ventral. Un examen histopathologique des tissus affectés a révélé la présence de bacilles alcoolo-acidorésistants par coloration de Ziehl-Neelsen. Une culture des tissus profonds confirma l'infection par des mycobactéries à croissance rapide, et le séquençage génétique caractérisa l'organisme comme étant Mycobacterium porcinum. Un traitement avec de la pradofloxacine et de la doxycycline permit une résolution clinique des lésions. Sept mois plus tard, à la suite d'une antibiothérapie continue, il n'y avait aucune récurrence locale ni de signe clinique associé avec une dissémination de l'infection. Ceci est la première description clinique d'une infection féline associée à ce microorganisme.Message clinique important :Ceci est la première description clinique d'une panniculite à mycobactérie chez un chat associée à Mycobacterium porcinum caractérisé génétiquement. Ce rapport de cas met en évidence une maladie qui peut représenter un défi diagnostique et de traitement pour les cliniciens.(Traduit par Dr Serge Messier).

Late pancreatic panniculitis in a simultaneous pancreas kidney transplant patient with failed allografts.

We present a rare case of pancreatic panniculitis in a 59-year-old male simultaneous pancreas-kidney (SPK) recipient with failed allografts. The patient presented with fever and painful erythematous nodules on his leg 1 month after stopping all immunosuppression. A thorough infectious and rheumatological workup was negative. He had pancreas rejection 4 years after SKP transplant and was restarted on dialysis after 14 years when his renal allograft failed due to chronic allograft nephropathy. His chronic immunosuppression (tacrolimus, azathioprine) was stopped and prednisone was weaned over 3 months at that time. A skin biopsy revealed saponification of the subcutaneous fat with inflammation pathognomonic of pancreatic panniculitis. Concurrent allograft pancreatitis confirmed with elevated lipase and a computed tomography scan finding of peripancreatic graft stranding and atrophic native pancreas. He was started on pulse steroid therapy for 3 days followed by oral taper. This resulted in dramatic resolution of all skin lesions and normalization of lipase levels within 1 week, followed by resumption of low-dose tacrolimus and azathioprine. This is an extremely rare occurrence of panniculitis in pancreas allograft after 10 years of pancreatic failure associated with stopping immunosuppression.

Post-erysipela panniculitis ossificans of the lower leg treated with pentoxifylline.

We report the case of a female patient who developed a firm, wooden-like, nonpitting edema of the left lower leg after a dermo-hypodermitis. The clinical picture was accompanied by intense pain, strongly impacting the patient's quality of life. A soft-tissue ultrasound demonstrated several millimetric hyperechoic linear lesions whose histopathological examination was conclusive for panniculitis ossificans. A conservative medical management with compression stockings associated with pentoxifylline 800 mg/day was prescribed with improvement of the edema and, in particular, a good pain control. To date, after a 2-year therapy with pentoxifylline, the leg wooden-like edema has substantially improved, despite the persistence of the well-known foci of ossification, and the pain has resolved, conditioning a substantial improvement of the patient's quality of life. No side effect has been observed during the routine follow up. Although there is no unanimous opinion in the literature about the effect of pentoxifylline on bone formation and osteogenic differentiation, pentoxifylline treatment proved to be beneficial in our patient both for the heterotopic ossification process and the pain control. We collected some of the data in literature about pentoxifylline effects and advanced some hypotheses to explain our results. Finally, we suggest that an anti-inflammatory and vasodilators drug such as pentoxifylline could be a possible alternative in heterotopic ossification disorders.

Pediatric Subcutaneous Panniculitis-like T-Cell Lymphoma With Hemophagocytosis Showing Complete Resolution With the BFM90 Protocol: Case Report and Review of Literature.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a distinct subtype of peripheral T-cell lymphoma associated with aggressive clinical behavior. Since its original description, it has continued to be a rare disease, and <200 cases have been reported in literature. We report an 11-year-old boy who presented with SPTCL and hemophagocytic lymphohistiocytosis (HLH) and responded to high-dose multiagent chemotherapy. He presented with steroid refractory erythematous, raised plaques over his face, trunk, and limbs over a period of 15 months treated elsewhere. Repeat evaluation in our center was consistent with SPTCL with features of HLH. He was initiated on therapy with the BFM90 protocol, which led to complete morphologic and biochemical remission. No single-best treatment regimen has been described for SPTCL with HLH in literature, and high-dose chemotherapy has shown good long-term remissions in the literature. The presence of SPTCL with HLH and systemic symptoms should prompt treatment with high-dose multiagent chemotherapy rather than Cyclophosphamide, Vincristine, Adriamycin, Prednisolone-like therapy. BFM90 is one such regimen that is well tolerated, and it can induce significant clinical and biochemical responses.

Neutrophilic Panniculitis in a child with MYSM1 deficiency.

Neutrophilic panniculitis (NP) with myelodysplasia has been described in adults but not in children. We report a case of NP associated with myelodysplasia in a child with MYSM1 deficiency, a newly described syndrome with primary immunodeficiency (PI), bone marrow failure, and developmental aberrations.

Exploring the combination of SSKI and topical heparin in a case of erythema nodosum migrans.

Erythema nodosum migrans (subacute nodular migratory panniculitis) is an uncommon type of panniculitis characterized by migrating subcutaneous nodules or plaque on the lower extremity. There are a very few cases of Erythema nodosum migrans reported and thus its appropriate treatment modality is not defined. We describe a case of a 30-year-old male with idiopathic erythema nodosum migrans which was manifest centrifugally spreading, slightly morpheaform erythematous plaque on the lower left leg. The patient was diagnosed initially and treated as a case of furunculosis with poor clinical response. The skin biopsy showed features consistent with subacute nodular panniculitis. Saturated Solution of Potassium Iodide along with topical Heparin successfully treated the patient, when the conventional treatment modalities failed. In a morpheaform centrifugally expanded plaque, erythema nodosum migrans should be kept in mind in the differential diagnosis, especially in the lower extremities in cases of unknown etiology.

Subcutaneous panniculitis-like T-cell lymphoma responsive to combination therapy with methotrexate and corticosteroids.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare condition that falls underneath the umbrella of primary cutaneous T-cell lymphomas (CTCLs). SPTCL can be very difficult to diagnose as it may mimic other subtypes of CTCL, such as γ/δ T-cell lymphoma (TCL), or other forms of panniculitis. Confirmation of diagnosis often requires immunohistochemical analysis and is essential for proper prognosis and therapeutic management. Herein, we present a case of SPTCL that mimicked lupus panniculitis and was successfully treated with prednisone taper and methotrexate.