reimbursement, general and administrative expenses, a $0.4 million increase in intangible asset amortization and earn-out expense, and a $0.4 million increase in research and development expenses. The $0.4 million increase in non-cash intangible amortization and non-cash earn-out expense was primarily attributable to the increase in intangible assets associated with the AffloVest acquisition, partially offset by a $0.2 million decrease in the estimated fair value of our earn-out liability.
Operating income was $3.8 million in the fourth quarter of 2021, compared to $7.0 million in the fourth quarter of 2020. Non-GAAP operating income in the fourth quarter of 2021 was $6.4 million, compared to Non-GAAP operating income of $7.8 million in the fourth quarter of 2020.
Other expense was $0.4 million in the fourth quarter of 2021, compared to other income of $1.2 million in the fourth quarter of 2020. The change in other expense/income was due to $1.2 million recognized in the fourth quarter of 2020 under the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) Provider Relief Fund to provide relief for lost revenues from the COVID-19 public health emergency.
Income tax expense was $10.9 million in the fourth quarter of 2021, compared to an income tax benefit of $3.9 million in the fourth quarter of 2020. The current year tax expense was driven by the recording of a full valuation allowance against our deferred tax assets.
Net loss in the fourth quarter of 2021 was $7.5 million, or $0.38 per diluted share, compared to net income of $12.1 million, or $0.61 per diluted share, in the fourth quarter of 2020. Non-GAAP net loss in the fourth quarter of 2021 was $5.5 million, compared to Non-GAAP net income of $11.8 million in the fourth quarter of 2020.
Weighted average shares used to compute diluted net income/loss per share was 19.8 million in the fourth quarter of both 2021 and 2020.
Adjusted EBITDA was $9.5 million in the fourth quarter of 2021, compared to $10.8 million in the fourth quarter of 2020.
Full Year 2021 Financial Results:
Total revenue for the twelve months ended December 31, 2021, increased $20.9 million, or 11%, to $208.1 million, compared to $187.1 million for the twelve months ended December 31, 2020. The increase in revenue was driven by an increase of $12.3 million, or 8%, in sales and rentals of the Flexitouch system, $5.1 million in sales of the recently acquired AffloVest respiratory therapy business and an increase of $3.5 million, or 15% in sales and rentals of the Entre system for the twelve months ended December 31, 2021. Revenue for the twelve months ended December 31, 2021, benefited from the initial stages of recovery from the COVID-19 pandemic during the first half of 2021, as well as an expanded prescriber base. However, revenue in the second half of 2021 was negatively impacted by the prolonged recovery from COVID-19, including the resurgence due to variants, which resulted in restricted access to clinics and hospitals and disrupted the recovery in patient visits versus the pre-COVID environment. In addition, the challenging labor market coupled with our vaccine policy impacted our ability to recruit and retain quality candidates for our direct sales force.