Voriconazole induced Periostitis :Mimicker of Inflammatory arthritis

Talha Khawar, MD

Rheumatology FellowLoma Linda University medical center,

Loma Linda, CA

Case description

• 31yo hispanic male with previous medical history of: – HTN– Brain Aspergillosis– Intracranial hemorrhage – Seizure from craniotomy– Ventriculo-peritoneal shunt– Gatrostomy tube placement and

tracheostomy

History of present illness• HPI: Nearly non-verbal at baseline(occasional “no”), wife/mother poor

historians, 5 week history of intermittent arm swelling and progressive DIP/PIP swelling, no clear aggravators/alleviators, not reported as painful, associated with maculopapular rash over upper chest

• PMH: Aspergillus fumigatus brain abscess, HTN, ICH, seizure disorder

• PSH: left frontal/parietal decompressive craniotomy and resection of the left frontal lobe mass, L endoscopic sinus surgery, frontal sinusostomy, a complete ethmoidectomy, sphenoidotomy, maxillary antrostomy, left orbital hardware removal, placement of ventriculostomy drain, and externalized VP shunt, tracheostomy placement, PEG placement

• Meds: amlodipine 10 mg , carvedilol 12.5 mg, citalopram 20 mg , docusate sodium 250 mg, ferrous sulfate 324/325, 65 mg TID, hydrocodone-acetaminophen 5-325 mg Q4, ipratropium-albuterol PRN wheezing, levetiracetam 1500 mg BID, voriconazole1,000 mg total q12, acetaminophen 325 mg/10.15 mL, bisacodyl 10 mg suppository, loperamide2 mg

History contd.• Allergy: NKDA

• PSocialHx: Past hx of tobacco, no IVDU/EtOH

Four years before admission: nasal polypectomy and removal of paranasalfungal mass• Three months before admission: loss of consciousness and seizure activity

– left frontal lobe mass with involvement of the left frontal sinus and extension through the roof of the orbit

• Left frontal/parietal decompressive craniotomy and resection of the left frontal lobe mass with surgical tissue cultures that grew Aspergillusfumigatus

• During the hospitalization: multiple surgical interventions for the aspergillusfumigatus brain abscess; On voriconazole since admission

• Acute respiratory failure requiring intubation and subsequent tracheostomy which was reversed later on

• PEG placement• Seizure episodes, started on anti-epileptics by Neurology• ICH resulting in right hemiparesis

Physical Exam• Temp: 98-99.7°F, Heart Rate: 92, Respirations: 16, Blood

Pressure: 142/80 mmHg, SpO2: 98 %• General appearance - chronically ill appearing, lethargic but

easily arousable, diaphoretic • Mental status - lethargic but easily arousable, does not follow

commands, opens eyes spontaneously • Eyes - right pupil sluggish but reactive, dilated, left pupil

round and reactive• Neck - supple, no significant adenopathy• Lymphatics - no palpable lymphadenopathy, no

hepatosplenomegaly• Heart - normal rate, regular rhythm, normal S1, S2• Chest - clear to auscultation, no wheezes, rales or rhonchi• Abdomen - firm, unable to access TTP, BS+, PEG in place

• Physical Exam contd.

• Neurological - lethargic but easily arousable, does not follow commands, opens eyes spontaneously, right hemiplegia, withdraws left arm and leg to noxious stimuli

• Musculoskeletal - b/l hand MCP, DIP, PIP joint swelling, erythema present, worse on R, guarding behavior of R hand, no warmth

• Extremities - RUE pitting edema 1+, no edema b/l LE

• Skin - dry, fine maculo-pustular rash present over chest

7/2/2015 22:05

WBC

10.78

RBC

3.65 (L)

Hgb

10.3 (L)

Hct

31.6 (L)

MCV

86.6

MCH

28.2

MCHC

32.6

PLTS

360 (H)

7/2/2015 22:05

Glu, Random

86

Na

140

K

3.9

Cl

101

CO2

26

Anion Gap

13 (H)

BUN

9

CREAT

0.4 (L)

Ca

2.2

Tot Prot

7.3

Albumin

3.6 (L)

AST

39 (H)

ALT

31

Alk Phos

1495 (H)

Tot Bili

0.3

7/3/2015 00:32

Westergren

71 (H)

Lupus Anticoagulant Test

Negative

7/6/2015 15:00

Cysticercosis Ab, CSF

Extensive periosteal reaction involving the phalanges, metacarpals and carpal bones, predominantly adjacent to the joints (some examples along the ulnar aspect of the hand indicated by arrowheads)

Periosteal reaction along the lateral aspect of the distal fibula (arrows)

3 PHASE BONE SCAN

Prominent uptake adjacent to the joints throughout both hands, particularly involving the wrists, corresponding to the areas of periosteal reaction on the radiograph of the hand

Voriconazole• Triazole antifungal medication• Commonly used in immunocomprimized

patients: Invasive candidiasis, invasive aspergillosis

• Metabolized by hepatic cytochrome P450 (no dose adjustment is necessary for renal impairment)

• Transient visual disturbances, fever, rash(phototoxicity), vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, respiratory distress

• Inhibits the fungal cytochrome P450 enzyme 14α-demethylase, thereby inhibiting synthesis of ergosterol

• Voriconazole is a broad spectrum, synthetic second generation azole antifungal

• We describe an interesting case of painful arthralgias and periostitis in a young patient on long term voriconazole therapy

• Long term use of voriconazole has been described as causing a painful periostitis and hypertrophic osteoarthropathy of the long bones in various immunocompromised patient

• Such adverse reaction is thought to be closely associated with the serum fluoride levels which tend to be much higher in patients being treated with voriconazole compared to general population

• Subacute or chronic fluoride ingestion in the form of difluorophenyl fluoropyrimidin which is the chemical composition of voriconazole is thought to be responsible for causing periostitis and skeletal fluorosis

References • Voriconazole A Review of Its Use in the Management of Invasive Fungal

Infections Lesley J. Scott and Dene Simpson: Drugs 2007; 67 (2): 269-298

• Voriconazole: A New Triazole Antifungal Agent. Leonard B. Johnson1 and Carol A. Kauffman Clinical Infectious Diseases 2003; 36:630–7

• Periostitis Secondary to Prolonged Voriconazole Therapy in Lung Transplant Recipients Wang et al: American Journal of Transplantation 2009; 9: 2845–2850

• Voriconazole-induced periostitis after allogeneic stem cell transplantation

• John H. Baird American Journal of Hematology, Vol. 90, No. 6, June 2015

References• Voriconazole-induced periostitis in two post-transplant patients: Radiology

Case. 2013 Aug; 7(8):10-17

• Clinical Images: Voriconazole-induced periostitis deformans :

• Voriconazole Induced Nodular Hypertrophic OsteoarthropathyRheumatology Winter Clinical Symposium 2012

• Voriconazole-Induced Periostitis Causing Arthralgias Mimicking a Flare of Granulomatosis With PolyangiitisJCR: Journal of Clinical Rheumatology & Volume 19, Number 8, December 2013

• Medication-induced periostitis in lung transplant patients: periostitisdeformans revisited Lina Chen & Michael E. Mulligan Skeletal Radiol(2011)

Voriconazole induced Periostitis :�Mimicker of Inflammatory arthritis Case description History of present illnessHistory contd.Slide Number 5Slide Number 6Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 113 PHASE BONE SCANSlide Number 13VoriconazoleSlide Number 15Slide Number 16References References