Nodular fasciitis: a benign mimicker of soft tissue malignancies / Fascitis nodular: un imitador benigno de las neoplasias malignas de tejidos blandos

La fascitis nodular es una masa subcutánea, benigna, autolimitada, que puede simular un sarcoma de tejidos blandos en su presentación clínica e histopatológica. Debido a que la mayoría de las descripciones de esta condición provienen de pacientes caucásicos, es necesario enfatizar su existencia en poblaciones poco representadas en la literatura. Se presenta el caso de un paciente mexicano, masculino, de 49 años, quien fue inicialmente mal diagnosticado y tratado como quiste epidérmico. Tras la recurrencia de la lesión, se realizó una adecuada técnica de biopsia y estudios de imagen, confirmando el diagnóstico de fascitis nodular. El presente reporte resalta la importancia de abordar con cautela las masas subcutáneas que puedan simular tanto tumores benignos como malignos para mejorar el pronóstico de los pacientes.

Nodular fasciitis is a benign, self-limited, subcutaneous tumor that may resemble a soft tissue sarcoma both clinically and histopathologically. Since most descriptions derive from Caucasian patients, further awareness is necessary in underrepresented populations. Here, we present a case of nodular fasciitis in a 49-year-old Mexican male who had been misdiagnosed and mistreated as an epidermal cyst. After recurrence, an adequate biopsy and imaging studies confirmed the diagnosis of nodular fasciitis. This case illustrates the importance of properly studying subcutaneous masses that can mimic a wide array of benign and malignant tumors to improve overall patient prognosis.

Characteristics of Japanese patients with eosinophilic fasciitis: A brief multicenter study.

Eosinophilic fasciitis is a relatively rare cutaneous fibrotic condition affecting the deep fascia of the extremities, with or without peripheral blood eosinophilia. To examine the characteristics of Japanese patients with eosinophilic fasciitis, we conducted a brief, multicenter, retrospective survey at seven university hospitals. In total, 31 patients were identified as having eosinophilic fasciitis, among whom 30 patients fulfilled the Japanese diagnostic criteria. The male : female ratio was 2.3:1, and the mean age was 47.7 years. Three of the patients were under 20 years old. The possible triggering factors included muscle training, sports, walking or sitting for a long time, physical work, insect bite and drug. Co-occurrence of morphea was observed in nine cases (29%), and malignancies were associated in three (two hematological malignancies and one internal malignancy). Immunological abnormalities in the serum showed positive antinuclear antibody, positive rheumatoid factor, increased aldolase levels and increased immunoglobulin G levels. The patients were treated with either monotherapy or combination therapy by oral prednisolone (20-80 mg/day), methotrexate (6-10 mg/week), cyclosporin (100-150 mg/day), mizoribine, infliximab and phototherapy. Methylprednisolone pulse therapy was performed in six cases. By contrast, spontaneous improvement due to resting only was observed in two cases, and skin hardening was improved by withdrawal of the anticancer drug in one case. This study suggests several characteristics of Japanese patients with eosinophilic fasciitis, namely male predominance, rare pediatric occurrence, immunological abnormalities and coexistence with morphea. Systemic prednisolone is the first-line therapy, but pulse therapy is occasionally required for severe cases. The triggering events of physical stress are not so frequent as have previously been reported, and various factors or even unknown factors may be associated with the induction of eosinophilic fasciitis.

Gulf war illness, post-HPV vaccination syndrome, and Macrophagic Myofasciitis. Similar disabling conditions possibly linked to vaccine-induced autoimmune dysautonomia.

More than one-fourth of all Persian gulf war coalition soldiers remain seriously ill. Several epidemiological studies suggest a link between multiple vaccinations at the time of the military operation and the illness development. Macrophagic Myofasciitis and post-HPV vaccination syndrome are two newer controversial vaccine-related disabling ailments. OBJECTIVES: 1) To systematically review all original articles investigating the association of vaccines with gulf war illness, 2) To discuss gulf war illness, Macrophagic Myofasciitis, and post-HPV vaccination syndrome clinical similarities, 3) To discuss emergent pathogenetic mechanisms proposed for post-HPV vaccination syndrome that may be also relevant to gulf war illness and Macrophagic Myofasciitis. RESULTS: All original epidemiological studies (n = 11) found a positive association between vaccination and gulf war illness development. Chronic fatigue, widespread pain and cognitive impairment characterize the three syndromes under discussion. Anti-adrenergic receptor antibodies, dysautonomia and small fiber neuropathy have been recently described in patients with post-HPV vaccination syndrome. CONCLUSION: post-HPV vaccination syndrome, Macrophagic Myofasciitis, and gulf war illness analogy suggests that some vaccines or multiple vaccinations in a very short period of time may induce, in susceptible individuals, chronic pain, fatigue and dyscognition. Vaccine-induced autoimmune dysautonomia is hypothesized as the common pathogenetic mechanism for this symptom cluster. Further research on the presence of small fiber neuropathy, adrenergic receptor antibodies, and abnormal autonomic function tests in the three syndromes under discussion may help to elucidate this hypothesis.

An MRI study of immune checkpoint inhibitor-induced musculoskeletal manifestations myofasciitis is the prominent imaging finding.

OBJECTIVE: To assess: (i) the prevalence, and clinical and imaging characteristics of immune checkpoint inhibitor (ICI)-induced musculoskeletal immune-related adverse events (ir-AEs) in a prospective manner and (ii) whether serum levels of cytokines associated with the Th1/Th2/Th17 response are differentially expressed in patients with and without musculoskeletal Ir-AEs. METHODS: All patients treated with ICI who developed musculoskeletal manifestations were referred to the Rheumatology Department, and an MRI of the involved area(s) was performed. RESULTS: During the study period, a total of 130 patients were treated with ICIs. Of these, 10 (7.7%) developed ICI-induced Ir-AEs. The median time from ICI treatment since development of symptoms was 2.5 months. Three different patterns of musculoskeletal manifestations were found: (i) prominent joint involvement (n = 3); (ii) prominent 'periarticular' involvement (n = 4). These patients had diffuse swelling of the hands, feet or knees. MRI depicted mild synovitis with more prominent myositis and/or fasciitis in the surrounding tissues in all cases; (iii) myofasciitis (n = 3). Clinically, these patients presented with pain in the knee(s)/thigh(s), whereas MRI depicted myofasciitis of the surrounding muscles. Patients with musculoskeletal ir-AEs had significantly higher oncologic response rates compared with patients not exhibiting musculoskeletal ir-AEs (50% vs 12.5%, respectively, P = 0.0016). Cytokine levels associated with a Th1/Th2/Th17 response were similar between patients with and without musculoskeletal ir-AEs. Overall, symptoms were mild/moderate and responded well to treatment, with no need for ICI discontinuation. CONCLUSION: In our cohort, ICI-induced musculoskeletal manifestations developed in 7.7% of patients. Imaging evidence of myofasciitis was found in most patients, indicating that the muscle/fascia is more frequently involved than the synovium.

Eosinophilic fasciitis: From pathophysiology to treatment.

Eosinophilic fasciitis is a disease originally proposed as "diffuse fasciitis with eosinophilia" by Shulman in 1974. The patients with this disease often have history of strenuous exercise or labor a few days to 1-2 weeks before the onset. The chief symptoms are symmetrical, full-circumference swelling and plate-like hardness of the distal limbs. This is accompanied by redness and pain in the early stages, with many cases exhibiting systemic symptoms such as fever or generalized fatigue. The lesions have been observed extending to the proximal limbs, though never on the face or fingers. En bloc biopsies from the skin to the fascia show marked fascial thickening and inflammatory cell infiltration by the lymphocytes and plasma cells. Eosinophilic infiltration is useful for the diagnosis but is only seen in the early stages of the disease. Recently, "Diagnostic criteria, severity classification, and clinical guidelines for eosinophilic fasciitis" were published. This review article discusses about eosinophilic faciitis in detail, from its pathophysiology to the treatment.

Clinical Characteristics of Fibromyalgia in a Chronic Pain Population.

OBJECTIVE: To compare fibromyalgia (FM) characteristics among patients identified in a community-based chronic pain cohort based on traditional International Classification of Diagnoses 9th revision (ICD-9) diagnostic coding, with that of patients identified using a novel predictive model. METHODS: This retrospective study used data collected from July 1999 to February 17, 2015, in multiple chronic pain clinics in the United States. Patients were assigned to the FM case group based on specific inclusion criteria using ICD-9 codes or, separately, from results of a novel FM predictive model that was developed using random forest and logistic regression techniques. Propensity scoring (1:1) matched FM patients (cases) to nonmalignant chronic pain patients without FM (controls). Patient-reported measures (eg, pain, fatigue, quality of sleep) and clinical characteristics (ie, comorbidities, procedures, and regions of pain) were outcomes for analysis. RESULTS: Nine ICD-9 clinical modification diagnoses had odds ratios with large effect sizes (Cohen's d > 0.8), demonstrating the magnitude of the difference between the FM and matched non-FM cohorts: chronic pain syndrome, latex allergy, muscle spasm, fasciitis, cervicalgia, thoracic pain, shoulder pain, arthritis, and cervical disorders (all P < 0.0001). Six diagnoses were found to have a moderate effect size (Cohen's 0.5 < d > 0.8): cystitis, cervical degeneration, anxiety, joint pain, lumbago, and cervical radiculitis. CONCLUSIONS: The identification of multiple comorbidities, diagnoses, and musculoskeletal procedures that were significantly associated with FM may facilitate differentiation of FM patients from other conditions characterized by chronic widespread pain. Predictive modeling may enhance identification of FM patients who may otherwise go undiagnosed.

Morphea and Eosinophilic Fasciitis: An Update.

Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud's phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.

Childhood macrophagic myofasciitis: A series from the Indian subcontinent.

INTRODUCTION: Macrophagic myofasciitis (MMF) is a rare disorder, reported mainly in European adults, with occasional childhood cases. We report a series of 6 patients with pediatric MMF from the Indian subcontinent. METHODS: Clinical details, creatine kinase levels, and results of electromyography are described for patients diagnosed with MMF. Fresh-frozen and formalin-fixed muscle biopsies were evaluated by hematoxylin-eosin staining, histochemistry, immunohistochemistry, and electron microscopy. RESULTS: Six of 2,218 muscle biopsies were diagnosed as MMF; patient charts were reviewed. The 6 patients were all children; all presented with hypotonia and/or motor delay. Mean age at diagnosis was 16.2 months. There were 4 boys and 2 girls. All had a history of hepatitis B vaccination. Histopathology revealed infiltration by sheets of large periodic acid-Schiff stain-positive histiocytes. Ultrastructural examination demonstrated needle-shaped crystals within histiocytes. One patient had a co-existent neuromuscular disorder, merosin-deficient congenital muscular dystrophy. CONCLUSIONS: MMF is a rare inflammatory myopathy that should be considered in the differential diagnosis of congenital myopathies in children. Muscle Nerve 56: 71-77, 2017.

Eosinophilia in Rheumatologic/Vascular Disorders.

Peripheral and tissue eosinophilia can be a prominent feature of several unique rheumatologic and vascular diseases. These diseases span a wide range of clinical features, histologic findings, therapeutic approaches, and outcomes. Despite the rare nature of these entities--which makes large-scale studies challenging--knowledge has continued to grow regarding their epidemiology, pathophysiology, and management. This review compares and contrasts 5 rheumatologic and vascular conditions in which eosinophilia can be seen: eosinophilic granulomatosis with polyangiitis (Churg-Strauss), immunoglobulin G4-related disease, diffuse fasciitis with eosinophilia, eosinophilia-myalgia syndrome, and eosinophilic myositis.

Nodular fasciitis: a retrospective study of 272 cases from China with clinicopathologic and radiologic correlation.

Our aim is to describe the largest series of nodular fasciitis (NF) with emphasis on the clinicopathologic and radiologic correlation. A total of 272 cases of NF were diagnosed between 2004 and 2014 at our institution. There were 160 males and 112 females with age ranging from newborn to 77 years (mean, 36 years). The upper extremity was the most common location (34%), followed by the head and neck region (24%), trunk (21%), and lower extremity (14%). By radiology, the lesion appeared as well-defined homogeneous mass with low or isodensity on computed tomography, homogenous hypointense or isointense on T1-weighted sequences, and heterogeneous intermediate-to-high signal on T2-weighted sequences. Although all cases were composed of short intersecting fascicles of uniform plump spindle cell, the cellularity and stromal components varied considerably between different cases. In intramuscular or deeply seated NFs, extension into adjacent skeletal muscles or structures was often noted. Immunohistochemically, all cases showed diffuse staining for smooth muscle actin and calponin, with consistent negativity for desmin, h-caldesmon, and ß-catenin. Of patients with available followed up information, only 1 experienced local recurrence due to incomplete excision. Our comprehensive study further demonstrated that NF had a wide clinicopathologic spectrum. Correlation with the radiologic features may help pathologists in arriving at an accurate diagnosis.

Forearm compartment syndrome as a result of eosinophilic fasciitis: case report.

Eosinophilic fasciitis is an uncommon scleroderma-like connective tissue disease, usually characterized by symmetrical and painful swelling and induration of the skin and thickened fascia infiltrated with lymphocytes and eosinophils. A middle-aged woman with follicular lymphoma being treated with chemotherapy presented with acute onset atraumatic forearm swelling and severe pain. The history, physical examination, and pressure measurements were consistent with compartment syndrome. Intraoperative biopsy of the forearm fascia confirmed eosinophilic fasciitis.

Distinctive clinical features in arthro-myalgic patients with and without aluminum hydroxyde-induced macrophagic myofasciitis: an exploratory study.

UNLABELLED: Macrophagic myofasciitis (MMF) is a specific histological lesion assessing the persistence of vaccine-derived aluminum oxyhydroxide in muscle tissue, at a site of previous immunization. Long-lasting MMF is usually detected in patients with arthromyalgias, chronic fatigue, and stereotyped cognitive dysfunction. MMF diagnosis requires muscle biopsy, an invasive procedure not suitable for the routine investigation of all patients with musculoskeletal pain. To help decision making in routine practice, we designed a retrospective analysis of 130 consecutive arthro-myalgic patients, previously immunized with aluminum-containing vaccines, in whom deltoid muscle biopsy was performed for diagnostic purposes. According to biopsy results, the patients were ascribed to either the MMF or the non-MMF group. MMF was diagnosed in 32.3% of the patients. MMF and non-MMF groups were similar according to both the injected vaccines and the delay between vaccination and biopsy. MMF patients had less frequent fibromyalgia than non-MMF patients (≥11 fibromyalgic tender points in 16.6 vs 55.5%, p < 0.04), and more often abnormal evoked potentials suggestive of CNS demyelination (38.5 vs 5.7%, p < 0.01). Predictive bioclinical scores based on simple variables such as the number of fibromyalgic tender points, arthralgias, and spinal pain, had sensitivity ranging from 50 to 88.1% and specificity from 36.4 to 76.1%. IN CONCLUSION: (i) most aluminum-containing vaccine receivers do not have long-lasting MMF in their muscle, but the prevalence of MMF among patients with arthromyalgia following immunization is substantial; (ii) patients with MMF have more CNS dysfunction and less fibromyalgic tender points than non-MMF patients; (iii) predictive scores may help to identify patients at high vs low risk of MMF.

[Nodular fasciitis of childhood: a clinicopathological analysis of 10 cases]. / Etude anatomoclinique de dix cas de fasciite nodulaire de l'enfant.

BACKGROUND: Nodular fasciitis rarely affects children. To date, apart from isolated cases, only two series comprising respectively 15 and six children have been reported. PATIENTS AND METHODS: We carried out a retrospective study of the clinical and pathological aspects of 10 cases of nodular fasciitis involving children under 15 years of age diagnosed at the pathology laboratory of the Necker Children's Hospital (Paris, France) between 1992 and 2006. RESULTS: In comparison with previously reported data, our study highlights four new factors: (1) nodular fasciitis affected girls more often than boys; (2) it occurred predominantly on the trunk; (3) follow-up showed a high recurrence rate (22%) after surgical removal; (4) immunohistochemical analysis revealed a high level of expression of p53 by tumour cells; this was much higher than in adults. DISCUSSION: The high expression of p53 in nodular fasciitis, which has never been described in children, seems to point towards its preneoplastic rather than reactive nature.

[Eosinophilic fasciitis: analysis of a series of 10 patients]. / Fascitis eosinofílica: estudio de 10 pacientes.

BACKGROUND AND OBJECTIVE: Eosinophilic fasciitis is an uncommon scleroderma-like syndrome with unknown etiology and pathogenesis. We report the clinical manifestations and response to therapy in a series of patients diagnosed with eosinophilic fasciitis. PATIENTS AND METHOD: The records of 10 eosinophilic fasciitis patients seen at our hospital between 1996-2004 were reviewed. RESULTS: Five patients were males, ages ranged from 20 years to 67 years, with a mean of 59 years. Patients were followed for 33.4 (27.1) months (SD). Nailfold capillaroscopy was near normal in all patients. Only one patient had antinuclear antibody positivity, and another had an autoimmune thyroiditis. No significant relationship was detected between the eosinophil count and the extent of skin induration. The clinical course was inadequate and the treatment response poor in patients with spreading cutaneous induration (p = 0.008). These patients had more often ventilatory restriction and perimyositis. CONCLUSIONS: Eosinophilic fasciitis does not always have a good prognosis. Ventilatory restriction, perimyositis and poor treatment response are not infrequent in a series of patients attended in a general hospital.

[Lessons from macrophagic myofasciitis: towards definition of a vaccine adjuvant-related syndrome]. / Myofasciite à macrophages et hydroxyde d'aluminium: vers la définition d'un syndrome des adjuvants.

Macrophagic myofasciitis is a condition first reported in 1998, which cause remained obscure until 2001. Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries. The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients. One third of patients develop an autoimmune disease, such as multiple sclerosis. Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis. Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy. Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid. Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile. It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome. Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms. Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome. Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome. Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis. Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome. Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant. If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide.