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History of present illness:
51 year old female who was seen at SLJ ER on 7/21/2020 with a 3 wk history of decreased appetite and generalized weakness and malaise. She had had prior colonoscopy and endoscopy showing only "mild colitis". She had been place on prednisone by her PCP. Her husband and daughter had recently tested positive for OVID 19 after separate trips to Mexico, but both had been essentially assymptomatic. An ultrasound of the abdoment was negative and CXR unrevealing. Her LFTs were initially elevated (SGOT 741 and SGPT 346, T. Bili 2.9). Her COVID 19 test was positive and was felt to be the cause of her symptoms and lab abnormalities. She was discharged home with appropriate instructtions for COVID19 symptom monitoring and self quarantine.
She returned to the ER on 7/25/20, unable to walk, with increasing weakness and numbness and loss of taste, with exam consistent with peripheral neuropathy. As before, she had no pulmonary symptoms. MRI of the C and T spine showed no cord compress, although there was some moderate to severe R NF stenosis at C5-6 and C4-5. MRI brain showed a small to moderate sized chronic left cerebellar hemisphere infarct and a small chronic R cerebellar and vermian infarcts.
She was admitted and treated with IV solumedrol for 3 days, with suspicion for an inflammatory polyneuropathy vs a paraneoplastic process. A lumbar puncture was benign, with normal cell count (2) and total protein (39). No improvement in the neurologic exam was noted and actually seemed to getting worse (legs 1/5 and arms 2/5 distally, stronger proximally). Decreased sensation in the LEs and depressed DTRs. She was hypophonic.
She was treated with a course of IVIG, with no definite motor improvement. She was treated with PLEX. No definite improvements noted.
She was treated with a 2nd course of IVIG 8/19/20, with minimal improvement noted only.
She developed a retroperitoneal hematoma on CT scan. She was diagnosed with DIC (disseminated intravascular coagulation). Diagnosed with anemia and was transfused.
A paraneoplastic panel was negative. SPEP negative for any monoclonal protein. Acute hepatitis panel was negative. ANA was 1:40. Negative alpha 1 antitrypsin, smooth muscle, and mitochondria antibodies.
She developed issues with encephalopathy/delerium and had hallucination. She says that she doesn't remember a lot about her acute hospitalization in the beginning. These symptoms were also attribuied to COVID19.
She had multiple electrolyte abnormalites which were replaced. Elevated lipase. Had AKI diagnosed and this has resolved. Treated with IV antibiotic for UTI
Her echocardiogram showed an EF of 34%, with some areas of hypokinesis, seen by cardiology with the impression of viral myopericarditis vs ischemic cardiomyopathy. She was treated for acute systolic heart failure.
She has not had an EMG/NCV test yet.
She was discharged to Brookdale SNF in Carmel Valley on 8/23/20. There she has shown some slow motor improvements in function, though still non-ambulatory, but felt now to be able to tolerate 3 hr/day of PT/OT. AFO's have been provided. Resolved DTI of the R heel. She has developed some painful nodules in the in the medial thighs bilaterally of unclear etiology. She has had multiple negative COVID 19 tests, the latest one last week. A repeat UTI (E. coli) has been treated with Keflex, completed 10/9/20. **On 10/13/2020 we admitted her to our ARU for rehab. She had the painful nodules to her medial and lateral thighs x greater than 3 weeks with no change in tissue color. on 10/14/2020 - I got a panic call from the nurse who was describing painful purple lesions to her rt thigh. Everyday she presents with more involvement and necrosis to bilateral thighs medial lateral and now lower legs. any thoughts.
Past medical/surgical history: As above. Hypoalbuminemia. Hypomagnesemia, on replacement. Anxiety (on bupropion). Mixed anemia. Fatty infiltration of liver. Left adrenal adenoma.
Cutaneous Vasculitis - Hemorrhagic skin necrosis- ?
Oct 17, 2020 by Kim Posten, RN
6 replies
Cathy Milne
APRN, MSN, CWOCN-AP
I am hoping my colleagues will also comment....
It’s been my experience that COVID skin changes occur after the acute event -in both symptomatic and asymptomatic patients.... given that this patient has has a stormy course with exposure to many pharmacological agents and her past medical history also places her at risk for other atypical ulcerations. She should have a biopsy of the lesions...and read by a dermatopathologist - as there can be many different etiologies such as leukocytoclastic vasculitis, calciphylaxis,etc. Has she has exposure to warfarin?
Oct 17, 2020
Elaine Horibe Song
MD, PhD, MBA
Hi Kim

Thanks for sharing this case. Cathy's answer is on point in my opinion - a skin biopsy for histopathology would help elucidate the diagnosis. In addition to Cathy's question regarding warfarin, is the patient on any sort of anticoagulant (e.g., oral anticoagulant or low molecular weight heparin)? The patient had disseminated intravascular coagulation (DIC). Is this resolved? How is the current DIC panel (PT, aPTT, fibrinogen, D-dimer, and platelet count) now compared to when DIC was diagnosed and upon admission? 

Given her history those skin manifestations could have several etiologies, but the exams above could help rule out purpura fulminans (post-infectious or due to DIC) which has been reported on COVID patients. Purpura fulminans is an acute syndrome of rapidly progressive hemorrhagic necrosis of the skin due to dermal vascular thrombosis. Skin necrosis begins in a region of dermal discomfort/pain. It usually involves the skin and subcutaneous tissue. Skin biopsy typically allows for definitive diagnosis.  

Also, as a side note - may or may not be relevant to her current status, since she has had multiple negative COVID 19 tests: this patient has hypomagnesemia, adrenal adenoma and inflammatory polyneuropathy. Curious to know how the serum aldosterone and IL-6 levels are/were, that is, if her adrenal adenoma is clinically silent or not. There are reports of COVID patients with primary aldosteronism due to adrenal adenoma, which led to more severe COVID symptoms, due to stimulation of IL-6 production. One of the manifestations was inflammatory polyneuropathy. 

Resources:
 https://www.sciencedirect.com/science/article/pii/B9780323476614000423https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26382
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404500/
https://cdn.ymaws.com/npiap.com/resource/resmgr/white_papers/COVID_Skin_Manifestations_An.pdf
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746263/https://www.aacc.org/cln/cln-stat/2020/june/4/disseminated-intravascular-coagulation-in-covid-19-insights-from-the-front-lines
https://ashpublications.org/blood/article/135/23/2033/454646/COVID-19-and-its-implications-for-thrombosis-and
Oct 17, 2020
They did a biopsy today of her right thigh not my first preference but they sent it for pathology as well as numerous other test I asked them to include direct immunofluorescent. we’re waiting to see if that can happen. We also sent her for every lab test that was on Wound reference under Cutaneous necrosis so were waiting to see! Honestly - hopefully will get her transferred to a tertiary facility with rheumatology and dermatology services available!!!
please continue to provide any insight as the patient is still an ARU! At a community-based hospital! we are unable to get dermatology consult or rheumatology consults. 😳🤮
Oct 17, 2020
Samantha Kuplicki
MSN, APRN-CNS, AGCNS-BC, CWS, CWCN-AP, CRNFA
Clearly a complex case.
Has acute coagulopathy been ruled out? Doesn't really fit the bill for shower emboli, but a possible d/dx.
Are there any bullae present? Did you send any of the bx in Michel's media, if so?
Did they ever perform muscle bx to workup the acute neuropathy or schedule EMG?
Is she still on steroid?
Consider febrile neutrophilic dermatosis such as Sweet's Syndrome.
Has she had PET or CT to rule out myelodisplastic disorder?
Oct 18, 2020
Update photos - Has anyone used a Skin Substitute for vasculitis- on a recovering Covid +
JL3.jpg
May 11, 2021
Elaine Horibe Song
MD, PhD, MBA
Hi Kim,

Thanks for the follow up question! Wondering if this picture is related to the same patient described in the beginning of the thread? In any case, some items to consider: Have other interventions been tried out (e.g. standard therapy)? Are there interventions in place to control the underlying condition (e.g. steroids for vasculitis) and exacerbating factors? Depending on the care setting, CMS and other third parties require that appropriate wound care therapy be in place and documented for at least 4 weeks.

I've exchanged messages with some of our advisors (Cathy, Alex, Gene). While we haven't had a chance to use a skin substitute for vasculitis on a pt. recovering from COVID-19, we think it makes sense to do so, after adequately preparing the wound bed and if the patient doesn't have any contraindications. The wound is covered with slough and necrotic debris, so in order for a skin substitute to be beneficial, the wound would need to be cleaned/debrided. If infection is present, it'd need to be addressed first. The choice of cellular and/or tissue product would depend on the characteristics of the wound bed after adequate wound bed preparation. Depending on the wound characteristics, one option could be a CTP based on umbilical cord tissue and/or amniotic membrane, due to its anti-inflammatory properties. Other options include acellular matrices (see case reports below). See brands here: https://woundreference.com/app/features2?tid=18 and https://woundreference.com/app/features2?tid=20

Case reports:
https://journals.sagepub.com/doi/full/10.1177/2050313X20910599
https://www.azisks.com/wp-content/uploads/2018/03/SB300.003-A-Primer-on-Amniotic-Membrane-Regenerative-Healing.pdf
https://pubmed.ncbi.nlm.nih.gov/19703952/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495753/
https://www.researchgate.net/publication/44300382_The_use_of_a_dermal_substitute_and_thin_skin_graft_in_the_cure_of_lower_limbs_wounds_from_vasculitis_observational_study

Other resources:
https://woundreference.com/app/topic?id=cellular-andor-tissue-products
https://www.coordinatedcarehealth.com/content/dam/centene/policies/clinical-policies/CP.MP.185.pdf
https://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id109TA.pdf
May 12, 2021
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