Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

Severe Electrolyte Abnormalities and Distal Renal Tubular Acidosis in the Setting of Psoriatic Arthritis and Apremilast Use Emilie McKinnon, MD, PhD, PGY-1 1 , Brody M. Fogleman, OMS III 2 , Schuyler Nebeker, DO, PGY-1 1 , Kedareeshwar Sanjay Arukala, MD 1

1 Grand Strand Medical Center, Department of Internal Medicine, Myrtle Beach, SC 2 Edward Via College of Osteopathic Medicine - Carolinas, Spartanburg, SC

Abstract

Case Summary

Discussion

Patient Profile:

Differential Diagnosis: ▪ Multiple myeloma ▪ Hyperaldosteronism ▪ Malignancy ▪ Pituitary adenoma ▪ Hyperparathyroidism ▪ Nephrolithiasis ▪ Vitamin B9/B12 deficiency

Etiological Uncertainty: ➢ Literature suggests autoimmune

Background Context: We present a case involving a 73-year-old female with psoriatic arthritis and severe symptoms, ultimately leading to the diagnosis of Type 1 renal tubular acidosis (RTA) with potential associations with apremilast. Case Presentation: A 73-year-old female presented with a 4-week history of weakness, anorexia, and unintended weight loss. Despite an extensive diagnostic workup excluding various causes, the patient was diagnosed with Type 1 RTA, and targeted treatments resulted in improvement. Comments: Comparison with medical literature suggests a potential link between autoimmune diseases and Type 1 RTA. 5 Apremilast's reported association with Type 2 RTA 2 raises questions about its involvement in Type 1 RTA, highlighting the uniqueness of this presentation. Diagnosis: The final diagnosis is Type 1 RTA with moderate certainty, given the observed response to targeted treatment. The case underscores the need for further research to explore the connection between psoriatic arthritis, apremilast, and Type 1 RTA. RTA refers to tubular dysfunction causing electrolyte imbalances and non anion gap metabolic acidosis. Types 1, 2, and 4 are the most common. 3 Criteria Type 1 (Distal) Type 2 (Proximal) Type 4 Primary deficit Distal tubular acidification defect Proximal tubular acidification defect Aldosterone deficiency or resistance Urine pH >5.5 <5.5 Varies Serum bicarbonate <15 mEq/L <15 mEq/L Varies Serum potassium Low Low Normal-to-high Urine Chloride > 20 mEq/L <15 mEq/L Varies Table 1. Differentiating features between Type 1, 2, and 4 RTA.

➢ 73-year-old female with medical history: psoriatic arthritis, osteoporosis, hypertension, hyperlipidemia, gastric sleeve surgery, and gastroesophageal reflux disease. ➢ 4-week history of extreme weakness, anorexia, 40 lb. unintentional weight loss, nausea, vomiting, constipation, and two recent falls. ➢ Limited oral intake during the 2 weeks before admission, was currently undergoing anemia workup. ➢ Home medications: apremilast (switched from secukinumab one month prior), hydrochlorothiazide, lisinopril, biotin, vitamin D, vitamin B12, prenatal complete, and brain health supplement. ➢ Presenting vitals: HR 49/min, BP 142/81, RR 18/min, O 2 Sat 100% on RA, T 98.5 F. ➢ Physical exam: frail, cachectic, systolic ejection murmur, scaphoid abdomen, hypoactive bowel sounds, diminished muscle strength without focal weakness.

diseases as common causes of RTA, but associations with psoriatic arthritis remain unclear. 5 ➢ Apremilast, previously linked to Type 2 RTA 2 , could be a contributing factor. ➢ Hypercalcemia association with Type 1 RTA, typically with severe nephrolithiasis and hypercalciuria (not evident here). 7

Conclusion: ➢ This case details an intricate diagnostic path of Type 1 RTA, with coexisting psoriatic arthritis. ➢ The absence of a definitive etiology emphasizes the need for ongoing research, which should further investigate the interplay of factors contributing to Type 1 RTA. ➢ Our findings advocate for a comprehensive approach in understanding autoimmune-related renal manifestations and emphasizes the importance of continued monitoring of drug adverse events, even following FDA approval. ➢ Our patient was diagnosed with Type 1 RTA of uncertain etiology, possibly pharmacologically-induced by apremilast, similar to the findings reported by Perrone et al. detailing apremilast-induced Type 2 RTA. 2

Initial Lab Values:

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Wd, ϭϯ͘ ϲ Wd,ͲZW ф Ϯ ϵ хϮϬ ϭϮ хϭϬϬϬ

ϮϱͲsŝƚͲ ϵϳ͘ ϯ ϭ͕ ϮϱͲsŝƚͲ ϳϰ͘ ϭ ůĚŽƐƚĞƌŽŶĞ ф ϭ ZĞŶŝŶ ф Ϭ͘ ϭϲϳ DŽƌŶŝŶŐ ĐŽƌƚŝƐŽů х ϲϭ͘ ϲ

Ă Ϯн DŐ Ϯн WK ϰ ϯͲ

ƵƌŐƵŶĚLJ – ŚŝŐŚĞƌ ƚŚĂŶ ŶŽƌŵĂů ͮ ůĂĐŬ – ǁŝƚŚŝŶ ŶŽƌŵĂů ůŝŵŝƚƐ ͮ KƌĂŶŐĞ – ůŽǁĞƌ ƚŚĂŶ ŶŽƌŵĂů

Refined Diagnosis:

Imaging:

Further research warranted to solidify these associations

Possibly secondary to apremilast or psoriatic arthritis

MRI Head, and CT of chest, abdomen, pelvis remarkable only for small bilateral pleural effusions, small volume ascites without evidence of a contributory neoplastic process.

Type 1 (Distal) RTA

Literature Review:

Treatment:

➢ Psoriatic arthritis is a systemic inflammatory autoimmune disease. 4 ➢ Autoimmune diseases are a well-known cause of Type 1 RTA. Psoriatic arthritis itself is not a well-established cause. 5 ➢ Apremilast was approved by the FDA in 2014 for psoriatic arthritis. 6

➢ In one previous case report, apremilast was determined the cause of Type 2 RTA with a similar clinical presentation as we present here. 2 No studies have reported apremilast as the cause of Type 1 RTA.

References

1 Both T, Zietse R, Hoorn EJ, et al. Everything you need to know about distal renal tubular acidosis in autoimmune disease. Rheumatol Int . 2014;34(8):1037-1045. doi:10.1007/s00296-014-2993-3 2 Perrone D, Afridi F, King-Morris K, Komarla A, Kar P. Proximal Renal Tubular Acidosis (Fanconi Syndrome) Induced by Apremilast: A Case Report. American Journal of Kidney Diseases . 2017;70(5):729-731. doi:10.1053/j.ajkd.2017.06.021 3 Palmer BF, Kelepouris E, Clegg DJ. Renal Tubular Acidosis and Management Strategies: A Narrative Review. Adv Ther . 2021;38(2):949-968. doi:10.1007/s12325-020-01587-5 4 Chimenti MS, Caso F, Alivernini S, et al. Amplifying the concept of psoriatic arthritis: The role of autoimmunity in systemic psoriatic disease. Autoimmunity Reviews . 2019;18(6):565-575. doi:10.1016/j.autrev.2018.11.007 5 Ungureanu O, Ismail G. Distal Renal Tubular Acidosis in Patients with Autoimmune Diseases — An Update on Pathogenesis, Clinical Presentation and Therapeutic Strategies. Biomedicines . 2022;10(9):2131. doi:10.3390/biomedicines10092131 6 Fala L. Otezla (Apremilast), an Oral PDE-4 Inhibitor, Receives FDA Approval for the Treatment of Patients with Active Psoriatic Arthritis and Plaque Psoriasis. Am Health Drug Benefits . 2015;8(Spec Feature):105-110. 7 Ferris T, Kashgarian M, Levitin H, Brandt I, Epstein FH. Renal Tubular Acidosis and Renal Potassium Wasting Acquired as a Result of Hypercalcemic Nephropathy. N Engl J Med . 1961;265(19):924-928. doi:10.1056/NEJM196111092651902

➢ The primary treatment for Type 1 RTA is bicarbonate supplementation. 5

This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.

The patient provided written informed consent during her hospitalization for the utilization of her medical history and clinical findings for research and educational purposes. Patient-specific data were obtained from electronic medical records of Grand Strand Medical Center. The authors declare that they have no financial or competing conflicts of interest regarding this research.

Figure 1. illustrates the patient's serum potassium and bicarbonate levels during their hospitalization and the corresponding medical therapy utilized.

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2024 Research Recognition Day