Kohlert et al. Journal of Otolaryngology - Head and Neck Surgery (2019) 48:52 https://doi.org/10.1186/s40463-019-0369-0 CASE REPORT Open Access A case report of severe nasal ischemia from cold agglutinin disease and a novel treatment protocol including HBOT Scott Kohlert1,2* , Laurie McLean3,4, Dimitrios Scarvelis5 and Calvin Thompson4,6 Abstract Cold agglutinin disease (CAD) is a rare condition leading to blood agglutination and autoimmune hemolytic anemia. Cutaneous ischemia resulting from CAD in the head and neck is uncommon. Treatment regimens and outcomes vary widely in the literature and no clear protocol exists. This manuscript describes a patient with CAD who developed severe ischemia of the nose that resolved completely without sequellae following a medical regimen of aspirin, low molecular weight heparin, nitroglycerin ointment and hyperbaric oxygen therapy (HBOT). To our knowledge, this is the first reported case where nitroglycerin ointment or HBOT was successfully employed in the treatment of this complication. Keywords: Nasal ischemia, Acrocyanosis, Cold agglutinin disease, Hyperbaric oxygen Introduction Case presentation Cold agglutinin disease (CAD) is a rare condition leading HC is an 84 year old female who developed a faint blue to blood agglutination at cold temperatures and auto- discoloration of her nasal tip following hip arthroplasty. immune hemolytic anemia. The incidence of CAD is 1/ The discoloration was initially intermittent but worsened 1,000,000 people per year [1], and the disease accounts in the postoperative period. With concerns of worsening for 13–15% of auto-immune hemolytic anemias. Clinical acrocyanosis during rehabilitation, she was transferred manifestations can occur in colder weather and the to our institution for hematological management on pathologic antibodies can bind to RBC cells and cause postoperative day (POD) 9. agglutination at areas of lower body temperature (in- Initial assessment revealed a violaceous plaque involving cluding extremities). Cutaneous manifestations of CAD the entire nasal tip and distal dorsum (Fig. 1) with loss of include acrocyanosis [2] and Raynaud’s phenomenon [3]. sensation at the tip and pain to palpation of the skin at the Head and neck manifestations are uncommon [4–7]. periphery. There were subtle violaceous changes to the Cutaneous ischemia resulting from CAD acrocyanosis helical rims of the ears bilaterally (Fig. 1). Anterior rhinos- in the head and neck is uncommon, with tissue loss copy and flexible nasolaryngoscopy revealed normal nasal resulting in potential disfigurement. Management and mucosa and no evidence of septal perforation. outcomes are variable, often with subsequent tissue loss Her past medical history included: primary cold agglutinin (Table 1). Treatment regimens can include targeting disease (CAD), severe aortic stenosis, hypertension, dyslipid- underlying immune response, anticoagulants, and surgi- emia and hypothyroidism. Medications include: Nifedipine cal debridement. We describe the successful manage- XL, Levothyroxine, Oxazepam, Pantoloc, Pregabalin, Hydro- ment of this condition with vasodilators and hyperbaric morphone, Tramadol, Trazodone, and Warfarin. Warfarin oxygen therapy. was held and patient was on Enoxaparin in postoperative period. Family history included systemic lupus erythemato- sus(SLE).Shewasalifelongnon-smoker,withnohistoryof * Correspondence: [email protected] 1ENT Associates of East Texas, 1136 E Grande Blvd, Tyler, TX, USA recreational drug use. Her CAD had previously been treated 2CHRISTUS Trinity Mother Frances Health System, 800 E. Dawson, Tyler, TX, with trials of rituximab (last dose 1 year prior to presenta- USA tion) and high dose corticosteroids, although both Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kohlert et al. Journal of Otolaryngology - Head and Neck Surgery (2019) 48:52 Page 2 of 5 Table 1 Previous Case Reports of Head and Neck Cutaneous Ischemia Secondary to CAD Authors Involved Region(s) Treatment Regimen Outcome Poldre and collagues Nasal tip, toes, fingers Plasmapheresis, sulfinpyrazone, Loss of 8 toes, no comment regarding outcome (1985) [4] dipyridamole, prednisone of nasal tip ischemia Oh and colleagues Cheek, thigh ASA (100 mg/day), supportive wound care Partial resolution, with some necrosis leading to (2009) [5] permanent scarring Jeskowiak & George Ear Heparin, isoprost, plasmapheresis and Initial improvement, subsequently lost to follow (2013) [6] surgical debridement up Mishra & colleagues Cheeks, nasal tip, ears, hands Full text not available for this paper (2013) [7] and buttocks medications had been discontinued. Prior to transfer to our Management institution she was given Prednisone 100 mg po × 1 dose. Two units of pRBCs were transfused on admission. No The initial differential diagnosis included vasoocclusion further corticosteroids were administered. Amphoteracin from agglutination, vasculitis, SLE, cryoglobulinemia and B was initially administered, but discontinued after 1 day anti-phospholipid antibody syndrome. Warfarin skin ne- as the clinical picture was not felt to be consistent with crosis was considered, but found to be unlikely as it had an invasive fungal infection. been held prior to the arthroplasty and not restarted The Otolaryngology and Dermatology services were postoperatively. consulted for assessment. They recommended to monitor and await immunological testing results. Nasal ischemia progressed acutely on post-admission day (PAD) #3, in- Laboratory investigations volving the entire length of the dorsum, and the tip be- Hemoglobin 75 × 1012/L (ref.: 115–155), Platelets 417 × coming necrotic with central sloughing (Fig. 2). A midline 109/L (ref.: 130–380). INR 1.2, PTT 28. Autoimmune nasal biopsy was taken at the junction between normal workup including ESR, ANA, cANCA, pANCA, C3, C4, and ischemic tissue, revealing thrombotic vasculopathy in ENA, dsDNA, anti-cardiolipin, and lupus anticoagulant the superficial dermal capillaries with no surrounding in- within normal limits. Mildly elevated CRP: 12.5 mg/L flammatory response, most consistent with thrombotic (ref.: ≤ 10). Hepatitis C serology was negative. The cold occlusion of the microvasculature of the nose secondary agglutinin titre was 32, with a thermal amplitude of to agglutination. 22 °C. The DAT was 4+ with anti-complement and Given the rapid clinical decline and possibility of exten- negative DAT for anti-IgG. The peak titre during her sive tissue loss, a multimodal management protocol con- disease was 128, with a thermal amplitude of 32 °C. sisting of nitroglycerin ointment (2% q8h), ASA (160 mg Haptoglobin was diminished at 0.10 g/L and LDH was PO × 1, then 81 mg PO daily) and Enoxaparin (40 mg SC elevated at 288 U/ml, reticulocytes were elevated at q12h until PAD#9, and then 40 mg SC daily until dis- 188.4 × 109]/L, indicating ongoing hemolysis. charge) was initiated. Hyperbaric Oxygen Therapy (HBOT) Fig. 1 Post-admission day #1 Kohlert et al. Journal of Otolaryngology - Head and Neck Surgery (2019) 48:52 Page 3 of 5 Fig. 2 Significant worsening by post-admission day #3 was initiated urgently (Perry Sigma II, Dualplace Hyper- Discussion baric Oxygen Chamber, Perry Baromedical Corporation). Medical Management of Cold Agglutination Cutaneous HBOT consisted of 2.5 Atmosphere Absolute (ATA) for 90 Ischemia min TID for the first 24 h, then BID for 3 days, and finally Goals of management for cutaneous ischemia associated once daily for 9 days without complication. The patient with CAD are to prevent further agglutination and clot- underwent a total of 18 HBOT over a 2-week period. ting (anticoagulants, avoiding cold temperature, immuno- suppressants), and optimize perfusion to ischemic tissues (vasodilators). Outcome and follow up Heparin and ASA have both been extensively studied The patient progressively improved (Fig. 3), and was dis- in the treatment of acute thrombotic disease, and have charged on PAD#17 with a one-month prescription for both previously been used in the management of cutane- Nitro Paste BID. Prior to discharge the patient was tran- ous ischemia resulting from CAD [5, 6]. sitioned to Warfarin which she continued to take at Nitroglycerin (NTG) ointment is a vasodilatory agent that home. At the time of follow-up (PAD 43), had normal has been described in the treatment of Raynaud’ssyndrome nasal sensation and no pain. The nose showed no evi- [8], ischemic digital ulcers [9] and post-surgical skin flap dence of ischemia. There was a faint scar at the biopsy necrosis [10, 11]. Its use has also been reported for the site. The nose was no longer tender and she had management of iatrogenic tissue ischemia arising from regained normal sensation. Fig. 4 highlights the patient’s following arterial line insertion [12], inadvertent intravascu- clinical progression throughout her treatment. lar filler injection [13], and vasopressor use [14]. Potential Fig.