Histopathologic reaction patterns to differentially cross-linked hyaluronic acid fillers: A retrospective case series.

BACKGROUND: Hyaluronic acid filler reactions have been increasingly observed in recent years. Our study investigates whether the increased number of filler reactions observed since 2014 is associated with a specific histopathologic inflammatory pattern and type of filler. METHODS: The institution's dermatopathology electronic database was retrospectively searched for histopathologic reactions to hyaluronic acid from January 2014 to December 2019. The age, sex, type of filler, procedure, location, and histopathologic patterns were recorded. RESULTS: From 2014 to 2019, there were 15 cases of granulomatous reactions to hyaluronic acid filler. In 10 of these cases, there was a characteristic inflammatory pattern characterized by tightly cuffed palisades of histiocytes with varying numbers of eosinophils. Of the 11 cases in which the type of filler was known, all used Vycross technology, a novel manufacturing process in the production of hyaluronic acid filler. CONCLUSION: A characteristic histopathologic pattern of discrete foci of tightly cuffed palisaded granulomas with eosinophils is associated with fillers manufactured using Vycross technology.

Hexachlorobenzene-induced eosinophilic and granulomatous lung inflammation is associated with in vivo airways hyperresponsiveness in the Brown Norway rat.

We investigated whether the eosinophilic and granulomatous lung pathology that develops in Brown Norway (BN/SsNOlaHsd) rats upon feeding hexachlorobenzene (HCB) is associated with nonspecific in vivo airways hyperresponsiveness (AHR) to methacholine. To this end, female BN/SsNOlaHsd rats were exposed to diets with no supplementation or diets supplemented with 450 mg HCB per kg feed. On days 7 or 21 of exposure in vivo airways hyperresponsiveness to increasing concentrations of methacholine was assessed both by whole body plethysmography and by visual scoring. In addition, lungs were lavaged to count and differentiate lavage cells, and skin and lungs were processed for histology. Lungs of the control rats showed some scattered microgranulomas and by 3 weeks of control diet some rats showed rather extensive granuloma formation and perivascular and peribronchiolar infiltration of eosinophils, as well as increased responsiveness to methacholine. Oral exposure to HCB for 7 days caused a moderate perivasculitis, but no increase of total serum IgE levels and no AHR to methacholine was found. Prolonged HCB exposure for 21 days resulted in severe and extensive eosinophilic and granulomatous lung inflammation, a threefold increase of total serum IgE levels, and marked cholinergic AHR in all rats. Correlation analysis revealed a significant relation between the AHR and lung inflammation, as judged by granuloma formation and increased numbers of eosinophilic granulocytes in the lung interstitium, particularly around the bronchi and bronchioli. No correlation was observed between serum IgE levels and AHR. Data suggest that HCB induces AHR by stimulating eosinophilic lung inflammation and that the preexistent microgranulomas may predispose to development of the HCB-induced lung pathology.

Sephadex-induced granulomatous alveolitis in rat: effects of antigen manipulation.

A granulomatous alveolitis, with multinuclear cell formation combined with an eosinophilic peribronchiolitis, was achieved in rats by intratracheal administration of sephadex beads (G-200, Pharmacia, Sweden). The pattern of inflammation and the degree of postgranulomatous fibrosis were substantially dampened when the particles were dispersed by ultrasonification. The animals were analyzed with bronchoalveolar lavage and tissue morphology.

Phenytoin-induced systemic granulomatous vasculitis.

Much has been written about adverse effects accompanying the use of phenytoin. However, the rare occurrence of systemic vasculitis induced by this drug has only been the subject of sporadic case reports and has not truly been characterized as a definitive entity. The high fatality rate of this complication is a proof of its severity. A case of multiorgan necrotizing granulomatous vasculitis related to the use of phenytoin is reported and the clinicopathologic aspects of seven similar cases assembled from the literature are summarized and discussed. The most commonly affected patients are elderly black men who present with skin rash, fever, and, frequently, eosinophilia. Tissue examination discloses systemic vasculitis that is often granulomatous and involves mainly the liver, kidneys, and spleen. Immediate recognition of this diagnosis is stressed, since proper treatment may reverse a fatal clinical course.

Experimental production of pulmonary granulomas. IV. Eosinophilic granuloma.

Pulmonary granulomas induced in rabbits by the endobronchial instillation of mycobacterial chemical fractions were re-examined for eosinophilic infiltration. Delayed type hypersensitivity reactions either of tuberculin type or of wax D type did not induce but rather suppressed eosinophilic infiltration in the inflamed area, although some peptidoglycans which are antigenic for the induction of immediate hypersensitivity and fatty acid fractions were weak stimulators of eosinophilic infiltration. Bacterial endotoxin, LPS, was a potent stimulator. It was found that some long chain fatty acids can cause severe eosinophilic infiltration in the induced granulomas. Arachidonic acid was the most active of those examined, so the activity of its metabolites was tested and PGE2 was found to be most active. As the eosinophilic infiltration was markedly suppressed in animals treated with a cyclooxygenase inhibitor (aspirin), the stimulators of eosinophilic infiltration were not fatty acids themselves but their metabolites, PGE2 and some others. The site of permeation of eosinophils from the circulation was found to be arteriolar in the inflamed lung. The granulomatous lesion with eosinophilic infiltration in rabbits is discussed to shed light on the aetiology of eosinophilic granuloma in the human lung.

Drug-induced granulomatous hepatitis.

Granulomatous hepatitis is a generic histopathologic diagnosis seen in approximately 5 to 10% of liver biopsy specimens. In the past, tuberculosis and sarcoidosis have been most frequently incriminated, although numerous other infectious and noninfectious etiologies have been reported. We have studied 95 cases of granulomatous hepatitis representing 6% of 1500 liver biopsies performed over a period of 10 years. Although sarcoidosis accounted for approximately one-third of these cases, probable and possible associations with medicinal compounds were detected in 29%. Highly suspect drugs include antihypertensive, antirheumatic and analgesic, anticonvulsant, and antimicrobial agents, but any drug may act as a hapten by covalent binding with macromolecular protein. The morphologic features of drug-induced, immunologic granuloma have not been described in detail. In our experience, eosinophils are prominent in the early granulomatous reaction to medicinal compounds and under continued antigenic stimulation are accompanied by plasma cells. Eosinophils are rare to absent in tuberculous hepatic granulomas and, when present in significant numbers, militate strongly against sarcoidosis. Drug-induced granulomas are consistently noncaseous. Although Kupffer cell granulomas have many causes, they are not uncommon hypersensitivity reactions to medicinal drugs and may give rise to clinical illness. Our review suggests that the previous literature does not reflect the magnitude of drug-induced granulomatous hepatic disease and that many cases reported as "granulomatous hepatitis consistent with sarcoidosis," as well as many "undiagnosed" cases, have a drug etiology.

Chlorpropamide-induced granulomas. A probable hypersensitivity reaction in liver and bone marrow.

Anicteric hepatitis, associated with fever and exfoliative dermatitis, developed in a diabetic patient two weeks after intake of a long-acting sulfonylurea, chlorpropamide (Diabinese). Granulomas showing heavy infiltration with eosinophils were found in the liver and bone marrow. These were interpreted as manifestations of an allergic reaction. The clinical signs, abnormal laboratory findings, and hepatic lesions subsided spontaneously on withdrawal of the drug. Bone marrow changes, however, persisted seven months after cessation of the drug. To our knowledge, this is the first report of a patient with liver and bone marrow inflammation characterized by granulomas with eosinophilic infiltration following intake of chlorpropamide.