Systemic Sarcoidosis
Meg Mangin, R.N. February 15, 2014
Mary is a 55 year old female Wife, mother and grandmother Employed part-time as a Registered Nurse Unremarkable childhood medical history Mother died age 90, father died age 85 Vital signs WNL Normal weight Physically fit for her age
Paresthesia left foot Slow onset beginning Jan 1999 Plantar surface numbness & tactile hypersensitivity Asthenia of toes Reduced mobility of foot Poor balance
Persistent acne since teens Adhesive capsulitis (Rx NSAIDS & PT) Various cutaneous lesions Achilles tendinitis Arthralgia Rhinitis Presumed uveitis
Red eye not improved w/abx; responded to cortisone drops
GERD
June 2001 -local neurologist : Lyme titer negative Glucose normal Dx: tarsal tunnel syndrome No hx of mechanical obstruction
Rx: Neurontin, B vitamins & Mobic 6 month F/U x two
Neuropathy slowly increasing
Exam:
Absent left ankle jerk reflex Weakness flexor & posterior tibialis muscles Atrophy posterior compartment
Labs
Electrophoresis abnormal
Electromyography
Finding: Tibial neuropathy
MRI pelvis & left leg
Finding: Denervation & atrophy calf muscles
Nerve biopsy Declined
Plan
6 month F/U
Denervation & atrophy of the gastrocnemius muscle and muscles of the posterior compartment of the left lower leg.
Tibial mononeuropathy, etiology unknown Monoclonal gammopathy: Referred to Hematology Possible sarcoidosis: Referred to Pulmonology
small nodules Rt lobe, – “probable old granulomatous disease.”
Chest CT-Apr 2002
Lung biopsy
Declined
No respiratory sx
Plan: watch and wait
IgM kappa spike Fat aspirate GMI antibodies 24hr urine Cryoglobulin Cryofibrinofen Declined full body xrays
MGUS Negative for amyloids Negative Negative for protein Negative Normal Declined bone marrow Plan: 6 month F/U
Increased neuropathy symptoms Severe nocturnal leg cramps Tests: GM-1 antibody – negative Repeat CT chest w/contrast – no changes ACE negative Repeat MRI – no changes Conclusion:
Potential sarcoidosis
Plan: wait and watch
SYSTEMIC SYMPTOMS
Respiratory Ocular Neurological Dermal Musculo-skeletal Elevated ACE (40%)
DEFINITIVE DIAGNOSIS
Biopsy positive for granulomatous tissue Exclude other granulomatous diseases
ACE normal Idiopathic neuropathy Suspected uveitis Muscular-skeletal sx Light sensitivity Elevated SED rate Lymphopenia Hypergammaglobulinemia
Rosacea Pulmonary nodules Cutaneous anergy
Non-reactive Mantouxs
Anemia of chronic disease Presumptive diagnosis: Systemic sarcoidosis
Lt foot neuropathy Leg cramps Fatigue Arthralgia Ankles, knee, hip, tailbone, shoulder
Light sensitivity Scalp lesions
Facial acne Lightheadedness Brain Fog Memory lapses Difficulty concentrating
Nasal congestion Depression Irritability
Hypotension Podagra Stiffness Tooth pain Hair loss Upper backache
LLQ pain Dry eyes Night sweats
Asthenia Postural paresthesia hands Tinnitus
Wait and watch:
Neuropathy was worsening.
Implications of future treatment with steroids. Explore infection connection to inflammatory symptoms
Hx: fever due to cytokine release immediately post IV abx Hx: FUO during visit to Ecuador in 1993. Nurses are exposed to more pathogens & have a higher incidence of sarcoidosis.
In 2001, Dubois,et al, published an article, Sarcoidosis: genes and microbes - soil or seed?, in the WASOG journal Sarcoidosis, that concludes "one or more microbes behaving in a non-infectious fashion in a genetically predisposed individual trigger the sarcoidosis granulomatous response".
In 2002, The CDC published, in Emerging Infectious Diseases, a report from Vanderbilt University, titled Molecular Analysis of Sarcoidosis Tissues for Mycobacterium Species DNA. This study "provide(s) evidence that one of a variety of Mycobacterium species, especially organisms M. tuberculosis, is found in most patients with sarcoidosis".
Discontinued vitamin D supplements. Avoided sunlight as advised for sarcoidosis patients. Leg cramps diminished Fatigue lessened Eyes became extremely light sensitive - sunglasses required indoors
Tetracycline 500 bid po x 30 days
Some improvement in skin lesions
Probe was considered positive
25(OH)D 26 ng/ml
Not elevated despite vitamin D supplementation Suggests rapid conversion of 25(OH)D to 1,25(OH)2D by extra-renal tissues
1,25(OH)2D 38 pg/ml
Borderline high per data from Danish study of healthy women. Symptoms involve tissues not well-perfused by blood (nerve, joint, skin) Serum level may not reflect tissue level
40mg q8h Initial reaction to Benicar
Brief extreme mental disorientation following first dose Fatigue (and other sx) increased first week
Significant increase in energy level after one week
Probably due to decrease in 1,25(OH)2D
100mg Minocycline qod
This is higher that the currently recommended 25mg initial dose
Brief mild disorientation post 30 minutes of dose Described as feeling inebriated This response only lasted several weeks
Symptom exacerbations indicated Herxheimer reactions.
Marked increase in symptoms the day following Minocycline: Foot numbness Leg cramps Fatigue Joint pain Light sensitivity Lightheadedness
Symptoms improved: Fatigue Arthralgia Memory lapses Paresthesia Minocycline increased to 200mg qod po
This is higher than the currently recommend maximum dosing of 100mg qod
Herxheimer reactions became stronger.
Herxheimer reactions diminished
Bactrim DS qod added Herxheimer reactions intensified
Nasal congestion
Fatigue March 2003 Scalp lesions
Before Therapy
Foot numbness 0
50
100
Symptoms continued to dissipate: Sleeping better Fewer night sweats Clearer thinking Increased muscle strength left foot
Depression resolved Light sensitivity diminished Continued intermittent symptom exacerbation Continued gradual reduction in symptoms Chest x-ray – no changes
Neuropathy improved. Increased foot strength:
Ankle jerk reflex now present.
Persistent mild weakness of toe flexors. “No weakness of posterior tib or pronator longus or a gastroc per se.” Remains asymmetrical and essentially -2 to -3.
Zithromax trial ordered by neurologist.
Herxing increased as expected.
25-D 13 ng/ml Indicates good control of vitamin D intake 1,25-D 21 pg/ml Indicates return of kidney control of 1,25-D production
Benicar 40mg q6h po Low-dose oral antibiotics Minocycline 25-100mg qod Zithromax 31.50mg-250mg q10days Clindamycin 37.50mg to 150mg qod Demeclocycline 37.50mg to 150mg qod Bactrim 1/8 SS to full DS tablet qod
Antibiotic combinations alternated 1-3 at a time Maintained 25(OH)D 10-30 ng/ml to prevent immunosuppression
No adverse effects 100% symptom reduction Improved health: Reduction in C/C – neuropathy Resolution of many inflammatory symptoms Improved bone density
No progression in MGUS No dental work needed since therapy began Eyes clear & healthy Routine health screenings negative Physically active
