Corticosteroid‐triggered acute skeletal muscle loss in lipodystrophy: A case report

ABSTRACT

The potential liability to hypercatabolism in lipodystrophy remains to be fully elucidated. Here we report a 28‐year‐old Japanese woman with acquired generalized lipodystrophy, who presented with recurrence of panniculitis and anemia. After corticosteroid treatment was started, she showed rapid reductions in body weight and lean mass by 15% at maximum, accompanied by an elevated urea nitrogen/creatinine ratio, which recovered almost fully as the corticosteroid treatment was tapered and discontinued. She had multiple risk factors for hypercatabolism: lack of metabolic reserves, insulin resistance, and hyperglycemia due to lipodystrophy, lowered daily activity due to anemia, persistent inflammation, and wasting associated with panniculitis, and relatively insufficient energy and protein intake during hospitalization. More attention should be paid to the potential liability to hypercatabolism in patients with lipodystrophy, and to skeletal muscle loss as an adverse effect of corticosteroid treatment in patients at high risk, such as those with diabetes or decreased metabolic reserves.

Here we report a 28‐year‐old Japanese woman with acquired generalized lipodystrophy, who presented with a rapid reduction in muscle mass by 15% at maximum during the weeks just after corticosteroid treatment was started. She had multiple risk factors for hypercatabolism other than administration of catabolic corticosteroid: lack of metabolic reserves, insulin resistance, hyperglycemia, lowered daily activity, persistent inflammation and wasting, and relatively insufficient energy and protein intake. More attention should be paid to the potential liability to hypercatabolism in patients with lipodystrophy, and to skeletal muscle loss as an adverse effect of corticosteroid treatment in patients at high risk, such as those with diabetes or decreased metabolic reserves.

INTRODUCTION

Lipodystrophy is highlighted by over‐nutrition and ectopic hyperanabolism ¹ , but the potential susceptibility to under‐nutrition and liability to hypercatabolism remain to be fully elucidated, given that adipose tissue serves as a metabolic storage to cope with fasting ² . Corticosteroid treatment enhances catabolism ³ , and corticosteroid‐induced myopathy is one of the hypercatabolic states observed frequently in clinical practice. Here we describe a patient with lipodystrophy showing acute muscle loss after initiation of corticosteroid treatment.

CASE REPORT

A 28‐year‐old Japanese woman first presented with idiopathic panniculitis at the age of 8, which recurred four times thereafter. It was successfully managed with periodic corticosteroid treatment but fat loss progressed each time.

She presented with ileus due to the loss of mesenteric fat, fatty liver, dyslipidemia, and diabetes at the ages of 15, 19, 20, and 27, respectively, with acquired generalized lipodystrophy and steatohepatitis diagnosed at the age of 28. One month after starting treatment with pioglitazone for glycemic control, she presented with anemia which had never been a feature of her disease previously as well as subcutaneous masses, and required hospitalization.

Her delivery was normal, and she had no family history of lipodystrophy.

On admission, she presented with a low body mass index and fever (Table 1). A physical examination revealed multiple subcutaneous masses with tenderness in her face, neck, and abdomen. Laboratory data revealed anemia, inflammation, poor control of diabetes, and hypoadipokinemia, with normal kidney function, and bioelectrical impedance analysis confirmed decreased fat mass and normal soft lean mass (SLM) (Table 1, Figure 1). Bone marrow aspiration revealed bone marrow fibrosis, and skin biopsy findings were compatible with those of cytophagic histiocytic panniculitis (CHP), frequently comorbid with anemia ⁴ . CHP and subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) are known to be histologically similar ⁵ , ⁶ , but T‐cell receptor gene rearrangement testing showed that SPTCL was unlikely in this case.

Table 1.

Key laboratory data and other key findings on admission

Body height	154.8 cm
Body weight (BW)	46.4 kg
Body mass index	19.4 kg/m2
Body temperature	38.0°C
Hb	6.1 g/dL
CRP	4.53 mg/dL
Interleukin‐6	7.6 pg/mL (<6.0 pg/mL)
TNFα	7.6 pg/mL (0.6–2.8 pg/mL)
HbA1c	8.7%
Urea nitrogen	8.1 mg/dL
Creatinine	0.46 mg/dL
Total adiponectin	0.03 μg/mL (>4.0 μg/mL)
Leptin	1.0 ng/mL (4.8–7.9 ng/mL)
Fat mass (BIA)	2.2 kg
SLM (BIA)	40.3 kg
SMI (BIA)	6.9 kg/m2

Reference values are shown in brackets, if needed.

BIA, bioelectrical impedance analysis; SLM, soft lean mass; SMI, skeletal muscle mass index; TNF, tumor necrosis factor.

Figure 1.

The course of BW, body composition examined by bioelectrical impedance analysis (BIA), a protein catabolism marker, and dosage of corticosteroid treatment. Corticosteroid treatment was started on day 10 of hospitalization (PSL, 50 mg/day), and she was discharged on day 56 of hospitalization (PSL, 30 mg/day). The skeletal muscle mass index (SMI) at minimum was 6.0 kg/m². BW, body weight; PSL, prednisolone; SLM, soft lean mass; UN, urea nitrogen.

Just after corticosteroid treatment was started, her BW unexpectedly decreased by 5 kg or 10% during the first 2 weeks and 7 kg or 15% at maximum, accompanied by elevated urea nitrogen (UN)/creatinine ratio. The SLM was reduced by 6 kg or 15%, whereas the fat mass was reduced by just 1 kg, which was confirmed by computerized tomography (Figure 2). Corticosteroid treatment was gradually tapered, and her BW and SLM recovered almost fully (Figure 1).

Figure 2.

The representative computerized tomography images of abdomen and pelvis, before the recurrence (plain), just after the recurrence and before the admission (contrast enhanced), and during corticosteroid treatment (contrast enhanced; day 45 of hospitalization). Solid arrows indicate representative changes in skeletal muscle (intermediate density) and dotted arrows indicate representative changes in fat (low density).

DISCUSSION

Adipose tissue acts as a metabolic buffer ² , and thus, lipodystrophy could be liable to hypercatabolism, whereas corticosteroid treatment promotes lipolysis in adipose tissue ⁷ , and protein degradation in skeletal muscle ³ , ⁸ . In this case, corticosteroid‐induced myopathy appeared immediately without a compensatory period generally for 2 weeks or longer ⁸ . Despite the lack of classical risk factors for corticosteroid‐induced myopathy ⁸ , she had multiple risk factors for sarcopenia ⁹ , ¹⁰ : severe insulin resistance and subsequent poor glycemic control, lowered daily activity, and persistent wasting (Figure 3). Elevated inflammatory cytokines, interleukin‐6 and tumor necrosis factor (TNF) α, associated with CHP could have accelerated hypercatabolism in skeletal muscle ¹¹ , at least in some part. Inadequate nutrition is another risk factor ⁹ , and given the lack of metabolic reserve due to lipodystrophy, diet therapy mainly for diabetes (30–37 kcal/kg BW/day; protein, 1.3–1.6 g/kg BW/day) may have been insufficient (Figure 3), although the protein intake was almost within the range of 1.0–1.5 g/kg BW/day, generally recommended during corticosteroid treatment ¹² .

Figure 3.

A scheme to show potential risk factors for hypercatabolism and muscle loss in this case: backgrounds, such as severe insulin resistance and subsequent poor glycemic control due to lipodystrophy, lowered daily activity due to severe anemia, and persistent wasting and inflammation, in combination with interventions, such as administration of catabolic corticosteroid and relatively insufficient diet therapy (1,400 kcal/day or 30–37 kcal/kg BW/day; protein, 60 g/day or 1.3–1.6 g/kg BW/day).

In this case, SPTCL was considered not likely at that point, but careful attention should still be paid to the possibility of progression from CHP to SPTCL. The risk of muscle loss is deemed to be high, if the case progresses to SPTCL and corticosteroid is administered as a part of chemotherapy, given that malignancy is one of the major risk factors for corticosteroid‐induced myopathy ⁸ .

This case highlights not only the role of adipose tissue as a metabolic storage but also therapeutic issues, including the importance of skeletal muscle loss as an adverse effect of corticosteroid treatment, especially in patients with diabetes and those with decreased metabolic reserves, and potentially in those with malignancy and those receiving catabolic drugs including sodium‐glucose cotransporter 2 (SGLT2) inhibitors. The UN/creatinine ratio and body composition could be useful for detecting skeletal muscle loss. Lastly, optimal diet therapy during corticosteroid treatment should be elucidated, especially in patients comorbid with diabetes, in order to prevent not only weight gain and hyperglycemia but also skeletal muscle loss.

DISCLOSURE

T.S. reports personal fees from AstraZeneca, Daiichi Sankyo, Eli Lilly, Kissei, Kowa, Nippon Boehringer Ingelheim, Novartis, Novo Nordisk, Ono, Sanofi, Sumitomo, Takeda, and Teijin. H.S. reports a grant from Nippon Boehringer Ingelheim. N.K. reports personal fees from Daiichi Sankyo, Eli Lilly, Kowa, Mitsubishi Tanabe, MSD, Nippon Boehringer Ingelheim, Novo Nordisk, Ono, Otsuka, Sanofi, Sumitomo, Taisho, and Teijin; grants and endowments from Daiichi Sankyo, Eli Lilly, Kowa, Mitsubishi Tanabe, MSD, Nippon Boehringer Ingelheim, Novo Nordisk, Ono, Sanofi, and Sumitomo. K.U. reports personal fees from AstraZeneca, Bayer Yakuhin, Daiichi Sankyo, Eli Lilly, Kowa, Mitsubishi Tanabe, Nippon Boehringer Ingelheim, Novo Nordisk, Ono, Sumitomo, and Taisho; grants and endowments from Nippon Boehringer Ingelheim, Kyowa Kirin, Mitsubishi Tanabe, Novo Nordisk, Ono, Sanofi, Sumitomo, and Takeda; consulting fees from Abbott, AstraZeneca, Bayer, Kyowa Kirin, Mitsubishi Tanabe, Sumitomo, and Terumo. T.K. reports lecture fees from Astellas, AstraZeneca, Daiichi Sankyo, Eli Lilly, Fujifilm Toyama Chemical, Kowa, Kyowa Kirin, Mitsubishi Tanabe, MSD, Nippon Boehringer Ingelheim, Novartis, Novo Nordisk, Ono, Sanofi, Sumitomo, Takeda, and Teijin; consulting fees from Abbott, Medtronic, and Novo Nordisk; grants and endowments from Astellas, Daiichi Sankyo, Eli Lilly, Kyowa Kirin, Mitsubishi Tanabe, MSD, Nippon Boehringer, Novo Nordisk, Ono, Sanofi, Sumitomo, Takeda, and Asahi Mutual Life Insurance. T.Y. reports personal fees from Abbott, Astellas, AstraZeneca, Bayer, Covidien, Daiichi Sankyo, Dojindo Laboratories, Eli Lilly, Fujifilm Toyama Chemical, Kissei, Kowa, Kyorin, Kyowa Kirin, Mitsubishi Tanabe, MSD, Musashino, Nippon Becton Dickinson, Nippon Boehringer Ingelheim, Novartis, Novo Nordisk, Ono, Roche, Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo, Taisho, Takeda, Teijin, Terumo, and Viatris; grants and endowments from Aero Switch Therapeutics Inc, Astellas, AstraZeneca, Daiichi Sankyo, EA, Kowa, Kyowa Kirin, Minophagen, Mitsubishi Corporation Life Sciences, Mitsubishi Tanabe, MSD, Nippon Boehringer Ingelheim, Nipro, Novartis, Novo Nordisk, Ono, Sanofi, Sanwa Kagaku Kenkyusho, Shionogi, Sumitomo, Takeda, Taisho, Tosoh, and Asahi Mutual Life Insurance. The other authors have nothing to disclose. K.U., T.K., and T.Y. are Editorial Board members of Journal of Diabetes Investigation and co‐authors of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication.

Approval of the research protocol: N/A.

Informed consent: The patient provided written informed consent for publication of this report.

Registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.