A skeleton in a huff: insights in etiologies of osteosclerosis.

A 30-yr-old man developed right lower leg pain and a palpable solid mass. Radiographic imaging revealed a periosteal reaction with an exostotic mass arising from the right distal fibula. Generalized skeletal osteosclerosis with periosteal reaction was discovered on a radiographic skeletal survey. A biopsy of the right fibular mass revealed reactive woven bone. The patient was referred to a metabolic bone disease clinic, where laboratory values were consistent with secondary hyperparathyroidism and increased bone turnover. A DXA bone density scan revealed high bone density, with an L1-4 spine Z-score of +9.3, a left femoral neck Z-score of +8.5, and a total hip Z-score of +6.5. A dental exam revealed generalized gingival inflammation, teeth mobility, generalized horizontal alveolar bone loss and widening of the periodontal ligament space, increased bone density around the teeth, and thickening of the radicular lamina dura. An extensive evaluation was performed, with the result of a single test revealing the diagnosis. The differential diagnoses of osteosclerosis affecting the skeleton, teeth, and oral cavity are discussed.

A 30-yr-old man developed, over a short period, pain in his lower right leg accompanied by a hard mass. He also reported weight loss and night sweats for the past 6 months. After evaluation by his primary physician, an X-ray was ordered that reported a bony mass arising from the right fibula bone. A biopsy was performed of the mass, but no evidence of cancer or any other specific abnormality was found. The patient was then referred to a bone disease specialty clinic. Laboratory tests revealed a large increase in how quickly the patient's skeleton was remodeling, affecting the balance of bone formation and removal involved in maintaining a healthy skeleton. A bone density scan reported that the patient had very dense bones. Other unusual changes were also discovered in a dental exam, suggesting bone thickening. After an extensive evaluation, a single blood test revealed the cause of the fibular bone mass and dense bones.

1,1-Difluoroethane Hydrocarbon Cardiomyopathy.

1,1-Difluoroethane (DFE) cardiomyopathy results from the direct inhalation of toxic halogenated hydrocarbons. We present a case series of acute DFE cardiomyopathy illustrating the typical presentation of severe DFE cardiomyopathy along with a detailed description of its mechanism of injury. (Level of Difficulty: Advanced.).

Skeletal fluorosis secondary to harmful inhalant use.

INTRODUCTION: Inhalants are common household items that may be abused for the desired effect of euphoria. Skeletal fluorosis is an uncommon and debilitating bone disorder caused by excess fluoride deposition. We report a case of skeletal fluorosis from chronic inhalation of an electronic duster product containing 1,1-difluoroethane. CASE: A 33-year-old male with inhalant use disorder presented to the emergency department with prominent bilateral hand swelling and long bone deformities. The patient reported five years of inhaling "surf onn.© electronic duster" (1,1-Difluoroethane). Diagnostic testing demonstrated urine fluoride 64.5 mg/L (ref <3) and serum fluoride 1.8 mg/L (ref <0.13). Radiographs demonstrated diffuse periosteal new bone formation and sclerosis consistent with skeletal fluorosis. CONCLUSION: Skeletal fluorosis is an uncommon complication of inhalant use disorder with products containing fluoride.

Periarticular calcifications containing giant pseudo-crystals of francolite in skeletal fluorosis from 1,1-difluoroethane "huffing".

Inhalant use disorder is a psychiatric condition characterized by repeated deliberate inhalation from among a broad range of household and industrial chemical products with the intention of producing psychoactive effects. In addition to acute intoxication, prolonged inhalation of fluorinated compounds can cause skeletal fluorosis (SF). We report a young woman referred for hypophosphatasemia and carrying a heterozygous ALPL gene variant (c.457T>C, p.Trp153Arg) associated with hypophosphatasia, the heritable metabolic bone disease featuring impaired skeletal mineralization, who instead suffered from SF. Manifestations of her SF included recurrent articular pain, axial osteosclerosis, elevated bone mineral density, maxillary exostoses, and multifocal periarticular calcifications. SF was suspected when a long history was discovered of 'huffing' a computer cleaner containing 1,1-difluoroethane. Investigation revealed markedly elevated serum and urine levels of F-. Histopathology and imaging techniques including backscattered electron mode scanning electron microscopy, X-ray microtomography, energy dispersive and wavelength dispersive X-ray emission microanalysis, and polarized light microscopy revealed that her periarticular calcifications were dystrophic deposition of giant pseudo-crystals of francolite, a carbonate-rich fluorapatite. Identifying unusual circumstances of F- exposure is key for diagnosing non-endemic SF. Increased awareness of the disorder can be lifesaving.

Skeletal Fluorosis: A Case of Inhalant Abuse Leading to a Diagnosis of Colon Cancer.

Skeletal fluorosis is a long-term bone disease that develops when prolonged fluoride toxicity leads to osteosclerosis and bone deformities that result in crippling pain and debility. The disease is endemic to many countries due to environmental or industrial exposures. However, rare cases in the United States have been reported from various causes including heavy toothpaste ingestion, excessive tea consumption, voriconazole use, and inhalant abuse. Here, we present a case of a 41-year-old man who presented for weight loss and severe joint pains due to bony sclerotic lesions found on X-rays. Social history revealed that he had been recreationally inhaling compressed air dusters used for cleaning electronics. Owing to concern for malignancy, he underwent an extensive work-up which led to a diagnosis of colon cancer, but positron emission tomography/computed tomography (PET/CT) and bone biopsy were unexpectedly negative for metastatic bone disease. Further characterization of his lesions by skeletal survey led to a diagnosis of skeletal fluorosis secondary to inhalant abuse. As in this patient, the disease can be difficult for clinicians to recognize as it can be mistaken for various boney diseases such as metastatic cancer. However, once there is clinical suspicion for skeletal fluorosis, various tests to help confirm the diagnosis can include serum and urine fluoride levels, skeletal survey, and bone ash fluoride concentration. Treatment of skeletal fluorosis primarily involves cessation of fluoride exposure, and recovery can take years. Ultimately, further study is required to develop recommendations and guidelines for diagnosis, management, and prognosis of the disease in the United States.

Multi-organ system failure secondary to difluoroethane toxicity in a patient "huffing" air duster: a case report.

Inhalant misuse is a growing concern among Americans. According to recent reports by the National Institutes of Health and the Substance Abuse and Mental Health Services Administration, the prevalence of teenage inhalant misuse is increasing. Of the many household items that are "huffed", refrigerant-based propellant cleaners or air dusters, are one of the most misused. Although commonly referred to as "compressed air", refrigerant-based propellant cleaners contain harmful fluorinated hydrocarbons, such as 1,1-difluoroethane, that have significant toxic effects when inhaled. While the central nervous system is primarily affected, there are case reports of cardiovascular, renal, hepatic, and musculoskeletal injury secondary to 1,1-difluoroethane toxicity. However, there are few cases that have presented 1,1-difluoroethane toxicity leading to multi-organ system failure in adults with a long history of inhalant misuse. We present a unique case of multi-system organ failure secondary to 1,1-difluoroethane toxicity in a middle-aged female that was "huffing" a refrigerant-based propellant aerosol duster for more than three months. This case stresses the importance of obtaining a detailed social history to identify inhalant misuse in patients that present with acute illness of unknown etiology. This case also highlights the importance of early communication with toxicology professionals for treatment and supportive care recommendations in patients presenting the life-threatening 1,1-difluoroethane toxicity. Furthermore, this case demonstrates that 1,1-difluoroethane toxicity in the setting of "huffing" air duster has the potential to cause multi-organ system failure.

Acute Inhalant-Induced Atrial Fibrillation With Severe Hypocalcemia: A Case Report and Review of the Pathophysiology.

The recreational use of inhalants is associated with various detrimental health effects ranging from inebriation to cardiac arrest. It also presents a challenging clinical problem as the diagnosis is made by the presentation and patient's history, which is often difficult to obtain in an intoxicated or obtunded individual. The incidence of inhalant use is relatively high. National surveys have reported that nearly 21.7 million Americans aged 12 and older have used inhaled substances at least once in their lives. There is no reversal agent or antidote for inhalants and supportive care is generally recommended. We present a case of a young patient presenting with acute inhalant toxicity accompanied by atrial fibrillation with a rapid ventricular response and severe hypocalcemia.

Acute Refractory Hypocalcemia in a 51-Year-Old Male With a History of 1,1-Difluoroethane Inhalation.

Hypocalcemia is a common electrolyte derangement that is most associated with parathryoid hormone or vitamin D abnormalities. Less common causes that most providers are aware of include hyperphosphatemia, acute pancreatitis, chronic kidney disease, and sepsis. However, certain populations are at risk for less common, but no less dangerous, causes. One such cause is 1,1-difluoroethane, an organofluorine that is used as a propellant in aerosol sprays and is commonly abused. 1,1-Difluoroethane has been noted to cause severe hypocalcemia by accumulation of the metabolite fluorocitrate in tissues. Here, we present the case of a 51-year-old male with severe hypocalcemia and multiple rib fractures following a fall, with recent history of tibial fracture. The patient had a medical history of osteoporosis with numerous fractures and chronic steroid use. He admitted to using keyboard cleaner as an inhalant for the previous month, which was found to contain 1,1-difluoroethane. Previous case reports on 1,1-difluoroethane inhalation have not reported a patient with preexisting osteoporosis or refractory hypocalcemia.

Non-endemic skeletal fluorosis: Causes and associated secondary hyperparathyroidism (case report and literature review).

Skeletal fluorosis (SF) is endemic primarily in regions with fluoride (F)-contaminated well water, but can reflect other types of chronic F exposure. Calcium (Ca) and vitamin D (D) deficiency can exacerbate SF. A 51-year-old man with years of musculoskeletal pain and opiate use was hypocalcemic with secondary hyperparathyroidism upon manifesting recurrent long bone fractures. He smoked cigarettes, drank large amounts of cola beverage, and consumed little dietary Ca. Then, after 5 months of Ca and D3 supplementation, serum 25(OH)D was 21 ng/mL (Nl, 30-100), corrected serum Ca had normalized from 7.8 to 9.4 mg/dL (Nl, 8.5-10.1), alkaline phosphatase (ALP) had decreased from 1080 to 539 U/L (Nl, 46-116), yet parathyroid hormone (PTH) had increased from 133 to 327 pg/mL (Nl, 8.7-77.1). Radiographs revealed generalized osteosclerosis and a cystic lesion in a proximal femur. DXA BMD Z-scores were +7.4 and +0.4 at the lumbar spine and "1/3" radius, respectively. Bone scintigraphy showed increased uptake in two ribs, periarticular areas, and proximal left femur at the site of a subsequent atraumatic fracture. Elevated serum collagen type I C-telopeptide 2513 pg/mL (Nl, 87-345) and osteocalcin >300 ng/mL (Nl, 9-38) indicated rapid bone turnover. Negative studies included hepatitis C Ab, prostate-specific antigen, serum and urine electrophoresis, and Ion Torrent mutation analysis for dense or high-turnover skeletal diseases. After discovering markedly elevated F concentrations in his plasma [4.84 mg/L (Nl, 0.02-0.08)] and spot urine [42.6 mg/L (Nl, 0.2-3.2)], a two-year history emerged of "huffing" computer cleaner containing difluoroethane. Non-decalcified histology of a subsequent right femur fracture showed increased osteoblasts and osteoclasts and excessive osteoid. A 24-hour urine collection contained 27 mg/L F (Nl, 0.2-3.2) and <2 mg/dL Ca. Then, 19 months after "huffing" cessation and improved Ca and D3 intake, yet with persisting bone pain, serum PTH was normal (52 pg/mL) and serum ALP and urine F had decreased to 248 U/L and 3.3 mg/L, respectively. Our experience combined with 15 publications in PubMed concerning unusual causes of non-endemic SF where the F source became known (19 cases in all) revealed: 11 instances from high consumption of black tea and/or F-containing toothpaste, 1 due to geophagia of F-rich soil, and 7 due to "recreational" inhalation of F-containing vapors. Circulating PTH measured in 14 was substantially elevated in 2 (including ours) and mildly increased in 2. The severity of SF in the cases reviewed seemed to reflect cumulative F exposure, renal function, and Ca and D status. Several factors appeared to influence our patient's skeletal disease: i) direct anabolic effects of toxic amounts of F on his skeleton, ii) secondary hyperparathyroidism from degradation-resistant fluorapatite bone crystals and low dietary Ca, and iii) impaired mineralization of excessive osteoid due to hypocalcemia.

Acute Psychosis Following 1,1-Difluoroethane Inhalation.

Inhalants are often abused due to their ability to acutely induce feelings of euphoria. Difluoroethane is a toxic lipophilic hydrocarbon that crosses the blood-brain barrier and inhibits the central nervous system. Studies have shown the cardiac, renal, and respiratory effects it has when abused; however, our literature review yielded no previous report of acute psychosis after difluoroethane inhalation. In order to prevent poor outcomes by missed diagnosis, we present a case of difluoroethane-induced acute psychosis.

Inhalation of 1-1-difluoroethane: A Rare Cause of Pneumopericardium.

We report a case of a 32-year-old man with a past medical history of ethanol use disorder who was brought in unresponsive after inhaling six to 10 cans of the computer cleaning product, Dust-Off. After regaining consciousness, he endorsed severe, pleuritic chest and anterior neck pain. Labs were notable for elevated cardiac enzymes, acute kidney injury, and his initial electrocardiogram (ECG) revealed a partial right bundle branch block with a prolonged corrected QT interval (QTc). On chest X-ray as well as chest computed tomography, the patient was found to have pneumomediastinum, pneumopericardium, and subcutaneous emphysema. The patient's course was uneventful and he was discharged home two days later after extensive substance abuse cessation counseling. Intentionally inhaling toxic substances, also known as "huffing," is a dangerous new trend with significant consequences that clinicians need to be aware of and suspect in young patients presenting with chest pain. We present a rare case of pneumopericardium induced by inhalation of Dust-Off (1-1-difluoroethane).

Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance.

Multiple reports of toxic myocarditis from inhalant abuse have been reported. We now report the case of a 23-year-old man found to have toxic myocarditis from inhalation of a hydrocarbon. The diagnosis was made by means of cardiac magnetic resonance imaging with delayed enhancement. The use of cardiac magnetic resonance to diagnose myocarditis has become increasingly common in clinical medicine, although there is not a universally accepted criterion for diagnosis. We appear to be the first to document a case of toxic myocarditis diagnosed by cardiac magnetic resonance. In patients with a history of drug abuse who present with clinical findings that suggest myocarditis or pericarditis, cardiac magnetic resonance can be considered to support the diagnosis.

Cardiomyopathy from 1,1-Difluoroethane Inhalation.

Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

Volatile substance misuse deaths in Washington State, 2003-2012.

BACKGROUND: Volatile substance misuse (VSM - also known as huffing or sniffing) causes some deaths, but because there are no specific cause-of-death codes for VSM, these deaths are rarely tabulated. OBJECTIVES: Count and describe VSM deaths occurring in Washington State during 2003-2012. METHODS: We used the textual cause-of-death information on death certificates to count VSM-associated deaths that occurred in Washington State during 2003-2012. We extracted records that contained words suggesting either a method of inhalation or a substance commonly used for VSM, and reviewed those records to identify deaths on which the inhalation of a volatile substance was mentioned. We conducted a descriptive analysis of those deaths. RESULTS: Fifty-six deaths involving VSM occurred in Washington State during 2003-2012. VSM deaths occurred primarily among adults age 20 and over (91%), males (88%), and whites (93%). Twelve different chemicals were associated with deaths, but 1 of them, difluoroethane, was named on 30 death certificates (54%), and its involvement increased during the study period. Gas duster products were named as the source of difluoroethane for 12 deaths; no source was named for the other 18 difluoroethane deaths. CONCLUSIONS: Most VSM deaths occurred among white male adults, and gas duster products containing difluoroethane were the primary source of inhalants. Approaches to deter VSM, such as the addition of bitterants to gas dusters, should be explored.

Blood and exhaled air can be used for biomonitoring of hydrofluorocarbon exposure.

Various hydrofluorocarbons (HFCs) have replaced the ozone-depleting chlorofluorocarbons and hydrochlorofluorocarbons during the last decades. The objective of this study was to examine the usefulness of blood and breath for exposure biomonitoring of HFCs. We compared data on blood and exhaled air from a series of experiments where healthy volunteers were exposed to vapors of four commonly used HFCs; 1,1-difluoroethane, 1,1,1-trifluoroethane, 1,1,1,2-tetrafluoroethane, and 1,1,1,3,3-pentafluoropropane. All four HFCs had similar toxicokinetic profiles in blood with a rapid initial increase and an apparent steady-state reached within a few minutes. For all HFCs, the inhalation uptake during exposure was low (less than 6%), most of which was exhaled post-exposure. No metabolism could be detected and only minor amounts were excreted unchanged in urine. The observed time courses in blood and breath were well described by physiologically-based pharmacokinetic (PBPK) modeling. Simulations of 8-h exposures show that the HFC levels in both blood and breath drop rapidly during the first minutes post-exposure, whereafter the decline is considerably slower and mainly reflects washout from fat tissues. We conclude that blood and exhaled air can be used for biological exposure monitoring. Samples should not be taken immediately at the end of shift but rather 20-30 min later.