Management of granulomatous foreign body reaction to fillers with methotrexate.

BACKGROUND: Granulomatous foreign body reactions (GFBR) have been reported after injection with almost every soft tissue fillers, more commonly with non-biodegradable ones. Such granulomatosis is rare but can cause significant discomfort owing to their aesthetic and functional repercussions. OBJECTIVE: To determine whether immunomodulation with low doses of methotrexate is effective in the treatment of GFBR to filler material. METHODS: Clinical case series of four patients with severe, treatment-resistant GFBR to non-biodegradable fillers in the Department of Dermatology of Bordeaux University Hospital, Bordeaux, France, successfully treated with oral or subcutaneous methotrexate, 10-15 mg weekly during 6 months. Adverse events were monitored throughout the treatment once weekly the first month then once monthly the remaining 5 months. RESULTS: Four women with a mean age of 73.7 years (66-85 years) and nodularity of the face were included and treated up to 6 months. Histological findings were consistent with GFBR to liquid injectable silicone in 2 cases, polymethylmethacrylate in 1 case and hydroxyethylmethacrylate in the last case. The delay after injection of the filler material was from 17 to 30 years. In one patient, inflammatory lesions followed dental care. After 6 months of treatment with 10-15 mg once weekly, all patients were cleared. Three patients developed a mild hepatic cytolysis (grade 1 or 2). Methotrexate could be maintained in those 3 cases and was discontinuated after 6 months in all cases. Two patients developed recurrence of lesions, 28 and 9 months, respectively, after treatment stops, requiring reintroduction of treatment. The two other patients remained cleared after 6 months of follow-up. CONCLUSION: Low doses of methotrexate appear to offer a low-risk therapeutic alternative in resistant and severe GFBR to fillers. A prospective study with long-term follow-up is required to confirm these preliminary observations.

[Eruptive granuloma after injection of Ellansé® successfully treated using methotrexate]. / Granulomes après injection d'Ellansé®, résolutifs sous méthotrexate.

BACKGROUND: Collagen stimulators such as Ellansé® are soft tissue fillers able to induce nucleogenesis. We describe a case of eruptive foreign body granulomas following injection of Ellansé® that were successfully treated using methotrexate. CASE REPORT: A 47-year-old woman received injections of Ellansé® for the wrinkled aspect of her cheeks. She had previously undergone injections of hyaluronic acid on the nasolabial folds. Nine months after the Ellansé® injections, the patient consulted for the recent appearance of multiple nodules on her face. Histological analysis of one of these nodules confirmed the presence of foreign-body granulomas developed in contact with spherical gaps of a size substantially identical to the Ellansé® vacuoles. Methotrexate 10mg per week for 3 months followed by 20mg per week for 9 months resulted in complete regression of the nodules. DISCUSSION: Ellansé® is composed of two biocompatible and bioabsorbable polymers: carboxymethylcellulose, responsible for immediate volume creation, and polycaprolactone, which promotes collagen synthesis. However, any injected product can cause varying degrees of granulomatous reaction. Hyaluronic acid was previously injected at several other sites on the patient's face. These lesions were not the result of poor injection technique. CONCLUSION: Although collagen stimulators are biocompatible and bioabsorbable substances, the development of foreign-body granulomas, while rare, is still possible. Methotrexate resulted in significant regression of nodules as of the third month of treatment.

Effect of anti-inflammatory activity of ranolazine in rat model of inflammation.

BACKGROUND & OBJECTIVES: Inflammatory processes are a recognized feature of atherosclerotic lesions. Ranolazine inhibits the inflammatory markers such as C-reactive protein, interleukins-1 and -6 and tumour necrosis factor-alpha. The present study was planned to evaluate the effect of anti-inflammatory activity of ranolazine in acute and sub-acute models of inflammation in rats and compare the same with that of control (gum acacia 1%) and aspirin (standard anti-inflammatory drug). METHODS: Adult male Wistar rats (150-180 g) were used for the study. They were divided into three groups (n=6). One per cent gum acacia (control), aspirin (200 mg/kg body weight) and ranolazine (180 mg/kg body weight) were given orally. Acute inflammation was induced by injecting carrageenan in the left hind paw. Paw oedema volume and percentage inhibition were measured. Subacute inflammation was induced by implanting foreign bodies subcutaneously. Percentage inhibition of granuloma dry weight and haematoxylin and eosin stained sections of granulation tissue were studied. RESULTS: In acute and subacute model study, ranolazine significantly (P <0.01) decreased the paw oedema volume and granuloma dry weight as compared to control and it was comparable to that of aspirin and histopathological sections showed a decrease in granulation tissue formation as compared to control. INTERPRETATION & CONCLUSIONS: Ranolazine demonstrated significant anti-inflammatory activity in acute and subacute models of inflammation and needs further evaluation for its use in reducing atherosclerosis.

Filler Nodules: Inflammatory or Infectious? A Review of Biofilms and Their Implications on Clinical Practice.

BACKGROUND: The numbers of minimally invasive cosmetic procedures performed in the United States have steadily increased each year. Concurrently, the rates of filler complications have also increased. Delayed filler reactions and granulomas have recently been attributed to biofilm infections. OBJECTIVE: The biology and pathogenesis of biofilms, and their diagnosis, treatment, and prevention will be discussed. METHODS: The relevant and recent literature on delayed filler reactions and biofilms was reviewed. RESULTS: Increasing evidence implicates biofilm infections in the pathogenesis of delayed filler reactions. Therapeutic and preventative measures can be taken to minimize the occurrence of these potentially devastating consequences of dermal fillers. CONCLUSION: Awareness of biofilm infections is key in the assessment of filler reactions in order to ensure timely and accurate diagnosis and treatment.

Subhepatic mass occurrence after using oxidized and regenerated cellulose polymer in laparoscopic cholecystectomy: a case series.

BACKGROUND: Oxidized regenerated cellulose (ORC) is a bioabsorbable surgical hemostatic. We present the first prospective case series of circumscribed mass occurrence after using ORC in laparoscopic cholecystectomy. METHODS: Tabotamp (Ethicon, Inc., Somerville, NJ) in the form of tightly woven knitted patches was used to achieve hemostasis in 83 patients submitted to LC. RESULTS: A subhepatic mass was detected in five patients and radiologic characteristics were described. Abdominal contrast enhanced CT showed a heterogeneous soft-tissue mass. NMR was performed in one patient and showed a T2-weighted hyperintense mass. CONCLUSION: ORC retention after surgery is not uncommon at long-term follow-up. The radiologic characteristics of a suspected ORC retention mass can differentiate it from a neoplastic lesion, so that surgery can be avoided.

Anti-inflammatory Effect of Picrorhiza kurroa in Experimental Models of Inflammation.

Picrorhiza kurroa is an important medicinal plant in the Ayurvedic system of medicine. The root and rhizome of this plant are used for the treatment of various liver and inflammatory conditions. In the present study, we sought to investigate the anti-inflammatory activity of P. kurroa rhizome extract against carrageenan-induced paw edema and cotton pellet implantation-induced granuloma formation in rats. In addition, its immunomodulatory activity was evaluated in Complete Freund's Adjuvant-induced stimulation of a peritoneal macrophage model and lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Pretreatment with P. kurroa rhizome extract inhibited carrageenan-induced paw edema and cotton pellet-induced granuloma formation in a dose-dependent manner. This was associated with reduced levels of inflammatory cytokines (TNF-α, IL-1ß, IL-6) accompanied with increased anti-inflammatory cytokine (IL-10) in the serum and peritoneal macrophages. Additionally, P. kurroa rhizome extract inhibited inflammatory TNF-receptor 1 and cyclooxygenase-2 in Complete Freund's Adjuvant-induced activated peritoneal macrophages. Furthermore, P. kurroa rhizome extract treatment significantly inhibited iNOS and suppressed the activation of NF-κB through inhibition of its phosphorylation and by blocking the activation of IκB kinase alpha in lipopolysaccharide-stimulated RAW264.7 macrophages. Taken together, these results suggest that P. kurroa has anti-inflammatory activity that is mediated through the suppression of macrophage-derived cytokine and mediators via suppression of NF-κB signaling.

Minocycline for the treatment of cutaneous silicone granulomas: A case report.

Silicone oil injections are often used for soft tissue augmentation and local and general adverse effects occurring from a few months to 15 years after injection have been reported. Here, we present a case of delayed granuloma formation due to liquid injectable silicone with large extent of involvement, which precluded surgical removal. Our patient was successfully treated with minocycline, considering its anti-inflammatory, immunomodulating and antigranulomatous properties. This case presents minocycline monotherapy as a useful treatment option for the management of severe granuloma induced by silicone use when surgical excision is not possible.

Complications of injected vitamin E as a filler for lip augmentation: case series and therapeutic approach.

The strive for proficient cosmetic facial appearance is growing in the past decades. Fillers for tissue augmentation are gaining wide popularity. Uncertified products based on oleic solutions are applied by untrained staff, thus growing the risk for certain complications such as infections, allergic and irritant contact dermatitis, and lipogranuloma formation. We present a series of three cases lipogranuloma after liquid vitamin E injection for lip augmentation. In all cases, painful edema at the injected area followed the procedure. The patients were presented with erythema, firm indurations of the lips and the perioral skin, and tenderness. Histological examination of skin biopsies showed round-ovoid cavities of varying sizes, resulting in a Swiss cheese-like appearance, consistent with a lipogranuloma. In this paper, we propose a protocol for treatment of this specific complication with systemic corticosteroids and a broad spectrum antibiotics.

Granulomatous reaction to liquid injectable silicone for gluteal enhancement: review of management options and success of doxycycline.

Liquid injectable silicone (LIS) for cosmetic purposes has been widely available and commonly used for almost half a century. An increase in buttock augmentation procedures because of patients wanting to emulate the look of some celebrities has recently highlighted cases in the media of unsafe administration of liquid silicone injections. Severe complications including death have been reported. In this article, we report a case in which liquid silicone was injected in the patient's gluteal tissue resulting in granulomatous reactions in the surrounding tissues. The patient responded well to doxycycline, presumably because of both its antimicrobial properties and immunomodulatory effects.

Tattoo granuloma of the eyelid mimicking carcinoma.

A 68-year-old woman was referred to the Oculofacial Plastic and Reconstructive Surgery service for evaluation of a left upper eyelid lesion that was worrisome for carcinoma. The mass measured 8 × 8 mm; it was well-circumscribed, pink, and firm with distortion of the eyelid margin, central ulceration, and loss of the lashes. The patient denied previous surgery or trauma in this area, but she had a history of blepharopigmentation (tattoo eyeliner) of all 4 eyelids approximately 7 years prior. Incisional biopsy revealed inflammatory changes consistent with a localized reaction to the tattoo pigment granules. Local kenalog injection was attempted with improvement of the overall appearance but with persistent deformity including irregularity of the margin and loss of lashes. The persistent abnormal appearance was worrisome for an underlying carcinoma missed on the initial incisional biopsy and prompted a full-thickness wedge resection and reconstruction of the abnormal area. The results of biopsy of the excised tissue confirmed absence of malignant neoplasm and showed changes consistent with tattoo granuloma. Tattoo granuloma of the eyelid should be considered in the differential diagnosis of eyelid lesions worrisome for carcinoma in patients with a history of blepharopigmentation.

Illicit narcotic injection masquerading as acute pulmonary embolism.

A 23-year-old male presented from a nursing home with hypotension, tachycardia, diaphoresis and electrocardiographic evidence of right ventricular strain that was confirmed by echocardiography. His differential diagnosis included sepsis and pulmonary embolism. A high-resolution computed tomography scan demonstrated no pulmonary emboli but did demonstrate multiple bilateral pulmonary nodules. Upon questioning he admitted to injecting a long-acting narcotic that had been manually macerated, dissolved in saline, and injected through an indwelling intravenous line. Lung biopsy findings were consistent with cellulose-induced perivascular granulomatosis. Cellulose granulomatosis can be seen in patients who inject medications designed for oral use and should be considered in patients who present with acute pulmonary hypertension.

A unique case of foreign-body associated orbital myositis.

A 50-year-old woman presented with a 2-week history of diplopia and right-sided orbital pain with eye movement. Examination revealed an edematous, ptotic right upper eyelid with conjunctival hyperemia, proptosis, and significant limitation to upward and downward ductions on the right. MRI was significant for a homogeneously enhancing lesion within the superior rectus muscle. A laboratory evaluation seeking an infectious, inflammatory, or autoimmune process was nonrevealing. A diagnosis of orbital myositis was made, and the patient experienced significant improvement with oral corticosteroids. The patient's symptoms, however, recurred after attempts at a slow taper of the corticosteroids. An orbital biopsy of the lesion revealed fibroadipose tissue containing irregularly shaped yellow-white deposits birefringent under polarized light, suggestive of silica crystals. The patient denied any history of trauma or prior surgery. An intraorbital triamcinolone injection to the superior orbit allowed resolution of symptoms and a successful taper off systemic corticosteroids.

Use of a combination of prednisolone and rosuvastatin for treatment of a pyogranuloma in a dog.

CASE DESCRIPTION: A 6-year-old spayed female Miniature Dachshund was examined because of a 3-day history of anorexia and diarrhea. CLINICAL FINDINGS: A lump was detected during abdominal palpation. Biochemical abnormalities included increases in serum concentrations of total protein, globulin, and C-reactive protein (CRP). Abdominal radiography and abdominal ultrasonography revealed a mass on the caudal aspect of the right kidney. Exploratory laparotomy confimed the mass; however, it could not be excised because it was strongly adhered to surrounding tissues. Histologic examination of a tissue sample from the mass led to a diagnosis of pyogranuloma. TREATMENT AND OUTCOME: The dog was treated with rosuvastatin, but no improvement was evident. Administration of a high dose of prednisolone (1 mg/kg [0.45 mg/lb], PO, q 12 h) was initiated. The CRP concentration returned to within reference limits, and the mass gradually decreased in size. The prednisolone dosage was tapered to 0.14 mg/kg (0.064 mg/lb), PO, every 12 hours. However, once the low dosage of prednisolone was reached, CRP concentration and size of the mass increased. Rosuvastatin was subsequently combined with the low dosage of prednisolone. After 1 week of the combination treatment, the CRP concentration returned to within reference limits, and the mass was reduced in size. The mass eventually could not be detected ultrasonographically. CLINICAL RELEVANCE: A low dose of prednisolone was not effective against the pyogranuloma. However, administration of a low dose of prednisolone in combination with rosuvastatin caused decreases in CRP concentration and size of the pyogranuloma. Thus, statins may act as immunosuppressants.

[Oleoma: A case report with good response to tetracycline]. / Oleoma: Relato de caso com boa resposta à tetraciclina.

Oleoma or paraffinoma is defined as a foreign body granuloma that results from the injection of oily substances into the skin or subcutaneous tissue. We present a young patient with ulcerated lesions secondary to infiltration of oily material. He had undergone the injections with the aim of increasing muscle mass and definition. The treatment of these cases is quite complex, often with unsatisfactory results. The use of long-term oral tetracycline proved to be helpful.