Symptomatic Improvement in Cicatricial Pemphigoid of the Trachea Achieved with Laser Ablation Bronchoscopy

Elizabeth Benge MD¹, Vincent Tran MD², Nazanin Sheikhan MD¹, Sapna Bhatia MD³, Yi McWhorter DO⁴, John Collier MD³, Arnold Chung MD⁵

Departments of ¹Internal Medicine, ²Surgery, ³Pulmonology, ⁴Anesthesiology/Critical Care Medicine, and ⁵MountainView Cardiovascular and Thoracic Surgery Associates

HCA Healthcare MountainView Hospital 

Las Vegas, NV, USA 

Abstract

Cicatricial pemphigoid (CP) with tracheal involvement is a rare and potentially deadly condition. Here, we report the first case in which Nd:YAG laser (1064nm) laser ablation bronchoscopy was used to treat CP with tracheal involvement. Our patient is a 71-year-old male with a history of CP refractory to medical therapy affecting his trachea who presented to the emergency department with dyspnea. He ultimately underwent bronchoscopy with Nd: YAG laser (1064nm) laser ablation, which resulted in a temporary alleviation of his respiratory symptoms. A repeat laser ablation was planned in hopes of prolonging the patient’s remission, but due to interval changes in the patient’s airway anatomy, it was deemed unsafe. While our patient’s uniquely advanced disease was not amenable to further laser-mediated intervention, it is possible that patients with less advanced disease may experience better outcomes with similar therapy. This case shows the promise laser ablation could hold for patients with tracheal cicatricial pemphigoid.

Introduction

Cicatricial pemphigoid (CP) is a diverse group of subepithelial blistering disorders of the skin and mucous membranes (1,2). Tracheal involvement is a rare and deadly sequela of this disease class (3). We report the first case in which Nd:YAG laser (1064nm) laser ablation bronchoscopy was used as a treatment for CP with tracheal involvement. Of note, the terms cicatricial pemphigoid and mucous membrane pemphigoid are synonymous and are used interchangeably throughout this report.

Case Presentation

Our patient is a 71-year-old man with a history of CP affecting his left eye and trachea who presented to the emergency department with progressively worsening dyspnea.

The patient has a history of multiple bronchoscopies; the most recent one showed tracheal pemphigoid lesions partially obstructing his airway. His diagnosis of cicatricial pemphigoid had been made over fifteen years prior to the current presentation via biopsy and subsequent immunofluorescence staining. On admission, his respiratory rate was 21 breaths/min and his oxygen saturation was 97% on 50% Bipap: 14/8. He was admitted to the intensive care unit for evaluation and management of his acute hypoxic respiratory failure.

Initially, a fiberoptic bronchoscopy was performed under laryngeal mask airway (LMA) general anesthesia. Dense, dark-colored lesions were noted to be occluding most of the trachea, consistent with the patient’s history of tracheal CP (Figure 1).

Figure 1. Patient’s trachea demonstrating heavy burden of cicatricial pemphigoid lesions prior to any intervention

They were partially removed in a piecemeal manner with forceps instrumentation. After this procedure, the patient still required supplemental oxygen, oscillating between BiPAP and nasal cannula. Two days later, he was started on rituximab, which he had also received during previous relapses.

On hospital day four, our cardiothoracic surgery team performed bronchoscopy with laser ablation under LMA general anesthesia. After the procedure, the patient’s tracheal lesions had markedly decreased in size (Figure 2).

Figure 2. Patient’s trachea with reduced lesions status-post bronchoscopy with laser ablation.

He was also entirely weaned off supplemental oxygen.

In the following weeks, the patient’s symptom burden was significantly decreased. He reported an improvement in his quality of life and satisfaction with the procedure. A subsequent repeat laser ablation was planned at the three-month mark. This procedure was more technically challenging due to airway-narrowing caused by an increase in scar tissue from the initial laser ablation. Due to the risks imposed by the interval changes in the patient’s anatomy, we decided against further laser therapy. In the absence of laser treatments, the patient’s tracheal pemphigoid recurred and symptoms returned to their prior state. He currently receives interval fiberoptic bronchoscopies to partially remove his lesions when they threaten his airway.

Discussion 

In a study involving subjects with aggressive ocular CP, 81% of patients achieved clinical remission with rituximab therapy (4). Medical therapy had repeatedly failed to reduce our patient’s symptoms, making his case unique in both its rarity and refractory nature. With no other options, our team developed an innovative treatment modality in an attempt to offer our patient some symptomatic relief.

Previous case reports have shown the utility of low-level laser therapy in mucous membranous lesions (5-7). One study showed successful resection of an obstructive mass caused by CP and restoration of airway patency using a Holmium LASER (2100nm) (8-9). We decided to ablate/resect the inflammatory tissue using an Nd:YAG LASER (1064nm) given its medium penetration length (1-4mm), coagulopathic ability (high heme absorption), and decreased tissue destruction when compared to the Ho:YAG laser; which has a higher laser absorption coefficient with water.

To our knowledge, this is the first case report of successful treatment of cicatricial pemphigoid with Nd:YAG laser (1064nm) ablation therapy. This procedure resulted in immediate, although ultimately impermanent, improvement in our patient’s respiratory insufficiency. Our patient also reported an improved quality of life during the period of time the laser ablation therapy offered him symptomatic relief. He was able to attend his grandchildren’s’ soccer games and walk to the end of his driveway to get his newspaper, activities he had not be able to participate in for years.

While our patient’s improvement was temporary, his disease process was uniquely advanced. It is possible that patients with less advanced disease may experience longer periods of remission with laser-mediated therapy, or may be able to tolerate repeated laser ablation procedures. Importantly, our patient’s case demonstrates that laser therapy can significantly reduce the burden of pemphigoid lesions, and can lead to a better quality of life for a disease process with few alternative treatment modalities.

Conclusion 

Therapeutic fiberoptic bronchoscopy with laser ablation is a promising treatment for patients suffering from CP of the trachea. Future investigations should focus on optimizing the laser ablation technique to achieve safe and sustained results.

References

1. Fleming TE, Korman NJ. Cicatricial pemphigoid. J Am Acad Dermatol. 2000 Oct;43(4):571-91. [CrossRef] [PubMed]
2. Minaie A, Surani SR. Mucous Membrane Pemphigoid with Tracheal Involvement. Case Rep Pulmonol. 2016;2016:5749784. [CrossRef] [PubMed]
3. Kato K, Moriyama Y, Saito H, Koga H, Hashimoto T. A case of mucous membrane pemphigoid involving the trachea and bronchus with autoantibodies to β3 subunit of laminin-332. Acta Derm Venereol. 2014 Mar;94(2):237-8. [CrossRef] [PubMed]
4. You C, Lamba N, Lasave AF, Ma L, Diaz MH, Foster CS. Rituximab in the treatment of ocular cicatricial pemphigoid: a retrospective cohort study. Graefes Arch Clin Exp Ophthalmol. 2017 Jun;255(6):1221-1228. [CrossRef] [PubMed]
5. Oliveira PC, Reis Junior JA, Lacerda JA, Silveira NT, Santos JM, Vitale MC, Pinheiro AL. Laser light may improve the symptoms of oral lesions of cicatricial pemphigoid: a case report. Photomed Laser Surg. 2009 Oct;27(5):825-8. [CrossRef] [PubMed]
6. Yilmaz HG, Kusakci-Seker B, Bayindir H, Tözüm TF. Low-level laser therapy in the treatment of mucous membrane pemphigoid: a promising procedure. J Periodontol. 2010 Aug;81(8):1226-30. [CrossRef] [PubMed]
7. Minicucci EM, Miot HA, Barraviera SR, Almeida-Lopes L. Low-level laser therapy on the treatment of oral and cutaneous pemphigus vulgaris: case report. Lasers Med Sci. 2012 Sep;27(5):1103-6. [CrossRef] [PubMed]
8. Jalil BA, Abdou YG, Rosen SA, Dammad T. Mucous Membrane Pemphigoid Causing Central Airway Obstruction. J Bronchology Interv Pulmonol. 2017 Oct;24(4):334-338. [CrossRef] [PubMed]
9. Benge E, Yamaguchi L, Tran V, Sheikhan N, Bhatia S, Mcwhorter Y, Collier J, Chung A. Successful Treatment of Cicatricial Pemphigoid of the Trachea with Laser Ablation Bronchoscopy. Chest. 2021 Oct 1;160(4):A1999-2000 [Abstract]. [CrossRef]

Abbreviations

• Bipap: bilevel positive airway pressure
• CP: cicatricial pemphigoid
• Ho:YAG: holmium-doped yttrium aluminum garnet
• Laser: light amplification by stimulated emission of radiation
• LMA: laryngeal mask airway
• Nd:YAG: neodymium-doped yttrium aluminum garnet

Disclosures

Conflicts of Interest: The above listed authors have no conflicts of interest to declare.
Funding: 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.
This case was presented at the CHEST Annual Meeting that took place from Oct 17, 2021 – Oct 20, 2021 in a virtual format.

Cite as: Benge E, Tran V, Sheikhan N, Bhatia S, McWhorter Y, Collier J, Chung A. Symptomatic Improvement in Cicatricial Pemphigoid of the Trachea Achieved with Laser Ablation Bronchoscopy. Southwest J Pulm Crit Care. 2022;24(1):8-11. doi: https://doi.org/10.13175/swjpcc058-21 PDF 

Payer Coverage of Valley Fever Diagnostic Tests

Chloe E Grace Rose¹, Joshua E Kessler¹, Jennifer A Weisbrod¹, Brittanie V Hoang², Amy J Grizzle³, Jason T Hurwitz³, John N Galgiani^4,5

¹University of Arizona College of Pharmacy, Tucson, AZ USA; ²University of Arizona College of Science, Tucson, AZ USA; ³University of Arizona Center for Health Outcomes & PharmacoEconomic Research, Tucson, AZ USA; ⁴University of Arizona College of Medicine, Tucson, AZ USA; ⁵Banner-University Health Valley Fever Program, Tucson, AZ USA

Abstract

Background

The nonspecific symptoms of Valley fever, or coccidioidomycosis, hinders its proper diagnosis. This results in unnecessary health care costs and antibiotic usage. Thus, this study seeks to determine the coverage of the Valley fever diagnostic test as provided by Arizona insurance companies to increase early diagnosis rates.  

Methods

Through scripted messaging and telephone communications, we contacted 40 health insurance companies in Arizona about their coverage of CPT 86635 (antibody diagnostic assay for Coccidioides) without prior authorization under all plan types provided in both primary and urgent care settings. If prior authorization was required, we discussed the coverage of ICD-10 codes J18.9 (pneumonia, unspecified organism), J18.1 (lobar pneumonia, unspecified organism), or L52 (erythema nodosum).

Results

Of the 40 health insurance companies contacted, 25 did not answer our inquiries, most requiring member-specific information to share coverage data. The remaining 15 companies covered Valley fever testing, of which 4 required prior authorization for the ICD-10 codes of interest. Of these 15 companies, 14 provided coverage in primary and urgent care settings, and 13 provided coverage for all available plans.

Conclusion

All payers that provided information covered Valley Fever testing. Most of the insurance companies that were unable to answer our inquiry likely cover Valley fever testing, but were unable to share information with third party inquiries. Obtaining general coverage information is difficult, which can potentially impact patient care.

Abbreviation List

• CPT: Current Procedural Terminology
• ICD: International Classification of Diseases
• ELISA: enzyme-linked immunosorbent assay

Introduction

Valley fever (i.e., coccidioidomycosis) is caused by the fungus Coccidioides and infection occurs through inhalation of the airborne fungal spores. Symptoms of Valley fever infection can be similar to those of other respiratory illnesses. While many patients who are exposed to the fungus remain asymptomatic, about a third experience pneumonia, arthralgias, and skin rashes such as Erythema nodosum, which typically last many weeks to months. A small percentage have more progressive complications such as chronic fibrocavitary pneumonia or dissemination of infection beyond the chest.

Around 150,000 infections are estimated to occur in the United States each year, mostly from Arizona and California (1). Of those infected, 50,000 may seek medical attention with 10,000 to 20,000 accurately diagnosed as Valley fever (2). Nearly two-thirds of all diagnoses nationwide originate from Arizona where Valley fever is responsible for about a quarter of all community acquired pneumonia (3,4,5). Because the symptoms of Valley fever are similar to those of other respiratory illnesses, diagnosis and treatment is often delayed if a laboratory diagnosis is not pursued, most commonly by a simple blood test. For this reason, national guidelines recommend that patients should be tested for Valley fever if they have symptoms of pneumonia or Erythema nodosum and either live in or have recently travelled to areas where Coccidioides is found.

In addition to problems with under-diagnosing, there can also be long delays in reaching a diagnosis. It has been estimated that 43% of Valley fever cases take longer than one month to diagnose (6). A 2021 study reported that of 1,287 new Valley fever cases, only 12% were diagnosed in the primary care setting, and less than 1% in urgent care (7). The majority of cases were unnecessarily diagnosed during an average three-day hospital stay after patients received 14 antibiotic doses, contributing to increases in both bacterial resistance and healthcare costs (7). Promoting awareness of Valley fever testing, specifically in urgent care and primary care settings where patients often present due to symptoms, is important in order to avoid delays in diagnosis and treatment, especially in endemic areas.

Increasing Valley fever diagnosis rates could have numerous benefits. Routine serology testing in patients who are suspected to have pneumonia would help increase Valley fever diagnosis, and reduce antibiotic use, which is often used empirically in these patients without effect, since Valley fever is a fungal infection and does not respond to antibiotics. Some of the excess costs associated with Valley fever are due to long delays to identify Valley fever. Reductions in unnecessary healthcare costs due to repeated primary and urgent care visits, and hospital admissions could be expected. Lifetime costs for the 10,359 cases of Valley fever diagnosed in Arizona in 2019 were estimated at $736 million (8). This represents a potentially important target that could lead to cost savings for patients and the healthcare system.

The purpose of this research is to determine coverage of the diagnostic test for Valley fever by insurance payers in Arizona. This is in response to the frequently asked question by both patients and clinicians regarding whether testing would incur out-of-pocket costs, and thus be declined by patients. Findings from this research will inform healthcare providers about coverage of the Valley fever test in Arizona to help increase early diagnosis of Valley fever, improve patient outcomes, and reduce healthcare costs (7).

Methods

Design

This is a descriptive study designed to determine payer coverage of Valley fever diagnostic tests. We used scripted messaging and telephone communications to contact payer organizations directly. All communications aimed to answer the question: is the Current Procedural Terminology (CPT) code 86635, an antibody diagnostic assay for Coccidioides, covered without prior authorization in primary and urgent care settings? CPT codes refer to a set of medical codes created and maintained by the American Medical Association (AMA) to represent procedures and services. This CPT code was chosen because it encompasses all forms of Valley fever diagnostic tests, including complement fixation, immunodiffusion and enzyme-linked immunosorbent assay (ELISA).

While precise sensitivity and specificity has not been established for ELISA, it is thought to be highly specific and more sensitive than older methods (9). Serologic ELISA testing is done by reference laboratories and results are returned between two days and two weeks, depending upon the clinic’s location and procedures for send-out tests.  A rapid test is available, but it requires a CLIA-certified laboratory which is not normally on site in most clinics (10). Clearly a point-of-care test would improve diagnosis.

We attempted to elucidate coverage further by inquiring about plan types, coverage settings, and specific ICD-10 diagnostic codes. Plan type was identified as all, not specified, or other. Payers that did not specify the plan type or provided coverage information for the most basic plan were assumed to cover all plans. In addition, we focused on coverage in urgent care and primary care settings, which have the greatest potential for improving diagnoses. Lastly, if coverage was dependent upon diagnosis and required prior authorization, we inquired whether ICD-10 codes J18.9 (pneumonia, unspecified organism), J18.1 (lobar pneumonia, unspecified organism), or L52 (erythema nodosum) would qualify for coverage of CPT 86635.

Study Population

We identified payers based on a list of claims for CPT 86635 retrieved from Sonora Quest Laboratories, one of Arizona’s market share leaders among clinical laboratories (11). Claims data was provided by Brian Mochon PhD, Clinical Associate Professor at the University of Arizona College of Medicine, and System Medical Director of Clinical Microbiology and Infectious Disease Serology for Banner Health and Sonora Quest Laboratories. The claims list was generated from patient visits at Banner Health facilities across Arizona. Sonora Quest Laboratories processed the samples used in Valley fever diagnoses and billed payers using CPT 86635. We used this claims list to identify payers to contact after removing duplicate payer entries and third-party claims processors.

Data Collection

We used a predefined protocol to standardize the data collection process. When available, we contacted payers electronically through the use of built-in chat or messaging systems on the company websites, using a standardized message. We allowed 3 business days for a response. If they did not respond, did not provide an appropriate answer, or there was no messaging service available, we phoned the company using member or provider services. A copy of our data collection protocol is included in the supplemental materials (Figure S1).

Data collection and management used REDCap (Research Electronic Data Capture) hosted at The University of Arizona (version 11.3.4). REDCap is a secure, web-based software platform designed to support data capture for research studies (12,13). The list of variables obtained from communication with payer organizations included: payer name, method of communication used (message and telephone), department contacted, CPT 86635 coverage (including ICD-10 codes in the event of prior authorization), settings of coverage (urgent care, primary care, both), type of plan covered, and miscellaneous data including reason for non-disclosure of coverage. A copy of the complete data collection form is included in the supplemental materials (Figure S2).

Data Analysis

This is a descriptive study; no statistical significance testing was performed. Results are displayed as measures of frequency, including counts and percentages.

Results

Between 01/01/2021 and 09/21/2021 claims were submitted to 53 insurance payers. Duplicates and different plans under the same payer were merged and third-party claims processors were also excluded, resulting in 40 insurance payers for our study.

Data collection through contact with insurance companies occurred during September and October 2021. Of the 40 insurance payers identified, 12 (30.0%) had accessible online messaging via a messaging portal or email address. After messaging each of these payers with the scripted message, 6 responded. We contacted 35 (87.5%) insurance payers via telephone.

CPT 86635 was identified as covered in 15 (37.5%) of our communications (Figure 1).

Figure 1. Coverage of CPT code 86635 (Valley fever diagnostic tests) by 40 payers.

Of those 15 payers, 4 required prior authorization while 11 (73.3%) did not. All three of the ICD-10 codes (J18.1, J18.9, and L52) were accepted to obtain authorization. Those that did require prior authorization were either Department of Defense associated plans, or were not based out of Arizona, where coccidioidomycosis infections may not be as prominent.

Both the online message and phone script included differences in CPT coverage between an urgent care and primary care setting. Positive coverage responses that did not differentiate variations in coverage based on setting were recorded as covered in both urgent care and primary care. Of all positive coverages, 14 (93.3%) were covered in both urgent care and primary care and 1 (6.7%) did not specify if coverage was for both urgent care and primary care. Table 1 summarizes CPT coverage details.

Table 1. Coverage details for CPT code 86635 among payers (N = 40) ^a.

^aList of payers (N=40) included: AARP Medicare, Aetna, All Savers, Allied Benefits System, Allwell, Ambetter, American Indian Health Program, ASR Health Benefits, AZ Foundation for Medical Care, Banner Family Care, BCBS Alabama, BCBS AZ, Bright Health, Care 1st Wellcare, CHAMP, Cigna, GEHA, Health Net, Humana, Imperial Health Texas Inc., Intel Arizona Connected Care, Kaiser Permanente, The Loomis Company, Medicare, Mercy Care, Meritain, Molina Complete Care of AZ, Multiplan Unified Life Insurance Company, OneCare Wellcare Medicare Advantage, Oscar Health Plan, Philadelphia American Life, Railroad MCR, Sierra Health and Life, Steward Health Choice, Summit, Tricare, Triwest VAPC, United Health, United Healthcare Community Plan, and WellCare MCR.

Of the 15 covered communications, 13 (86.7%) covered all plans, while 1 (6.7%) communication did not specify variation between plans, and 1 (6.7%) was member-specific to one of our researchers and denoted as “other”.

Of the 40 insurers contacted, 25 (62.5%) were unable to provide coverage information for Valley fever testing. The majority required member-specific information in order to disclose coverage details about a contracted plan. Given we had no specific patient for each plan and were only making general inquiries on behalf of a physician, we listed these communications as “Unable to Determine”. None of the 40 payers indicated that CPT code 86635 was not covered.

Discussion

In this study, we obtained coverage information for Valley fever diagnostic tests from 15 of the 40 payers we contacted. Of note, none of the remaining 25 payers said CPT code 86635 was not covered under their plans, only that they could not provide information, largely because such information requires specific member identification for one of their plan holders. In addition, 4 of the total providers required prior authorization for the diagnostic. These providers were either Department of Defense associated plans or were not based out of Arizona or California. Since coccidioidomycosis is largely endemic to Arizona and California, it is not unreasonable for an out of state insurance provider to require a prior authorization for a condition that is not endemic to their population. However, some national providers and out of state providers did state they cover the diagnostic without a prior authorization.

The difficulty of obtaining general coverage information from an insurance payer quickly became apparent. We anticipated that some payers would not disclose coverage information, however, given that we were requesting information on behalf of a practicing physician, we did not anticipate this response from most payers. The lack of transparency in providing benefit information to potential patients or providers is concerning and may negatively impact patient care. However, based upon the favorable response we received from payers that did provide information, it is likely that most of the insurers unable to provide information do cover the Valley fever diagnostic test.

Our findings build upon literature describing the lack of diagnoses of Valley fever, predominantly in the urgent care setting. Pu et al. (2020) reported the total diagnosis of coccidioidomycosis was a mere 0.5% in the urgent care setting from 2017-2019. At the time of our study, we found no previous publications on payer coverage of Valley fever diagnostic tests. However, we identified similar methods utilized in the existing literature. Cohen et al. (2019) researched insurance policies for coverage of gender re-affirming surgeries via online and telephonic methods and identified policies for 124 of 150 payers (14). A report by Park et al. (2019) researched insurance coverage policies for multiple pharmacogenomic tests via online methods and identified policies for 33 of 41 payers (15). Both of these studies were able to identify a larger proportion of coverage from the identified payers than our current study, though Park et al. (2019) did highlight difficulties from a patient or provider perspective in identifying payer coverage (13).

Results, however, must be considered in light of several study limitations. Payers were limited to those that were available via claims data from Sonora Quest Laboratories for predominantly Arizona payers. In addition, the claims data were derived solely from patients seen at Banner Health facilities, excluding patients seen for diagnosis and claims filed outside of the Banner Health network. The actual population of Valley fever patients is likely larger and may have had different coverage patterns than we collected. This data source and focus on Arizona limits generalizability of findings. However, Valley fever is endemic to Arizona and the Southwestern region of the United States.

This study also faced data collection limitations. Although our communications were scripted, the payers’ representatives may have not had a similar procedure. We may have obtained different results based upon the individual who was communicated with, and this may have impacted our ability to gather information.

For this study, we assumed that confirming CPT 86635 coverage by the payer’s representative meant coverage was generalizable to all plan types offered by the payer and all care settings where a patient might be seen. If a payer did not specify variability in coverage based on plan or care setting, we assumed all plans and all care settings were covered without need for prior authorization. 

Due to barriers that often exist for patients to see a primary care provider in a timely manner, many patients’ first interaction for Valley fever is in an urgent care setting. There remains a need to educate these providers about the availability and coverage of tests for patients, as current lack of knowledge may negatively impact patient care by delaying diagnoses and potentially leading to hospitalization.  While insurance coverage or cost may or may not be a limiting factor for a provider to order the diagnostic test, cost could be a limiting factor for the patient. Education can be provided to providers about recognition and testing coverage for Valley fever. Patients could then be educated as well in recognition of symptoms and insurance coverage trends, which could increase total tests ordered. Increased testing rates could help identify Valley fever diagnoses sooner and more frequently. This study highlights an important step of identifying payer coverage for Valley fever diagnosis in an urgent care setting. These results may help to inform providers about insurance coverage for their patients and increase early diagnosis of Valley fever cases. Future research could build upon this study by incorporating provider knowledge and education in relation to the impact on patients presenting with Valley fever in urgent care and primary care settings.

Acknowledgments

The authors wish to thank Banner Health and Sonora Quest Laboratories for their contributions in providing claims information for this research.

Author Contributions Statement

BVH, CEGR, JEK, and JAW contributed to data collection. CEGR, JEK, and JAW drafted the manuscript. AJG, JTH and JNG provided edits and commentary on the manuscript. All authors contributed to research design.

References

1. Valley Fever Awareness. Centers for Disease Control and Prevention. Updated July 26, 2021. Accessed 12 October 2021. https://www.cdc.gov/fungal/features/valley-fever.html
2. Galgiani JN. Coccidioidomycosis (coccidioides species). In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 9th Ed. Philadelphia, PA: Elsevier; 2019.
3. Valley Fever Statistics. Centers for Disease Control and Prevention. Accessed 12 October 2021. https://www.cdc.gov/fungal/diseases/coccidioidomycosis/statistics.html
4. Kim MM, Blair JE, Carey EJ, Wu Q, Smilack JD. Coccidioidal pneumonia, Phoenix, Arizona, USA, 2000-2004. Emerg Infect Dis. 2009;15(3):397-401. doi:10.3201/eid1563.081007
5. Valdivia L, Nix D, Wright M, et al. Coccidioidomycosis as a common cause of community-acquired pneumonia [published correction appears in Emerg Infect Dis. 2006 Aug;12(8):1307]. Emerg Infect Dis. 2006;12(6):958-962. doi:10.3201/eid1206.060028
6. Donovan FM, Wightman P, Zong Y, et al. Delays in Coccidioidomycosis Diagnosis and Associated Healthcare Utilization, Tucson, Arizona, USA. Emerging Infectious Diseases. 2019;25(9):1745-1747. doi:10.3201/eid2509.190023.
7. Pu J, Donovan FM, Ellingson K, et al. Clinician Practice Patterns That Result in the Diagnosis of Coccidioidomycosis Before or During Hospitalization. Clin Infect Dis. 2020;73(7):e1587-e1593. doi:10.1093/cid/ciaa739
8. Grizzle AJ, Wilson L, Nix DE, Galgiani JN. Clinical and Economic Burden of Valley Fever in Arizona: An Incidence-Based Cost-of-Illness Analysis. Open Forum Infect Dis. 2020;8(2):ofaa623. Published 2020 Dec 28. doi:10.1093/ofid/ofaa623
9. Learn More about Who We Are. Sonora Quest Laboratories. Accessed 15 October 2021. https://www.sonoraquest.com/about/who-we-are/.
10. Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis. 2016;63(6):e112-e146. doi:10.1093/cid/ciw360
11. Donovan FM, Ramadan FA, Khan SA, et al. Comparison of a Novel Rapid Lateral Flow Assay to Enzyme Immunoassay Results for Early Diagnosis of Coccidioidomycosis. Clin Infect Dis. 2021;73(9):e2746-e2753. doi:10.1093/cid/ciaa1205
12. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377-381. doi:10.1016/j.jbi.2008.08.010
13. Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi:10.1016/j.jbi.2019.103208
14. Cohen WA, Sangalang AM, Dalena MM, Ayyala HS, Keith JD. Navigating Insurance Policies in the United States for Gender-affirming Surgery. Plast Reconstr Surg Glob Open. 2019 Dec 11;7(12):e2564. doi: 10.1097/GOX.0000000000002564. PMID: 32537307; PMCID: PMC7288898.
15. Park SK, Thigpen J, Lee IJ. Coverage of pharmacogenetic tests by private health insurance companies. J Am Pharm Assoc (2003). 2020 Mar-Apr;60(2):352-356.e3. doi: 10.1016/j.japh.2019.10.003. Epub 2019 Dec 13. PMID: 31843376.

Cite as: Grace Rose CE, Kessler JE, Weisbrod JA, Hoang BV, Grizzle AJ, Hurwitz JT, Galgiani JN. Payer Coverage of Valley Fever Diagnostic Tests. Southwest J Pulm Crit Care. 2021;23(6):155-61. doi: https://doi.org/10.13175/swjpcc052-21 PDF

A Summary of Outpatient Recommendations for COVID-19 Patients and Providers December 9, 2021

Richard A. Robbins MD¹

Stephen A. Klotz MD²

¹Phoenix Pulmonary and Critical Care Research and Education Foundation, Gilbert, AZ USA

²Division of Infectious Disease, Department of Medicine, University of Arizona College of Medicine, Tucson, AZ USA

We thought a follow-up to our original brief review of COVID-19 in February, 2020 might be useful. As we write this in early December 2021, we again caution that this area is rapidly changing and what is true today will likely be outdated tomorrow. We again borrowed heavily from the Centers for Disease Control (CDC)  CDC website and the NIH website which have extensive discussions over numerous pages covering COVID-19. Our hope is to condense those recommendations. We do not discuss inpatient care in any detail.

COVID-19 Variants

The initial steps of coronavirus infection involve the specific binding of the coronavirus spike (S) protein to the cellular entry receptors which are normally on a cell. These include human aminopeptidase N (APN; HCoV-229E), angiotensin-converting enzyme 2 (ACE2; HCoV-NL63, SARS-CoV and SARS-CoV-2) and dipeptidyl peptidase 4 (DPP4; MERS-CoV).

All viruses, but especially simple single-stranded RNA viruses like COVID-19, constantly change through mutation resulting in new variants (1). The variants vary in severity and infectivity. The CDC, World Health Organization (WHO), and other public health organizations monitor COVID-19 for emergence of new variants. Some variants emerge and disappear while others persist.

The Delta variant causes more infections and spreads faster than the original SARS-CoV-2 strain of the virus that cause COVID-19 (2). Delta is currently the predominant variant of the virus in the United States causing over 99% of infections (2). On November 24, 2021, a new variant of SARS-CoV-2, B.1.1.529, was reported to the World Health Organization (WHO). This new variant was first detected in specimens collected on November 11, 2021 in Botswana and on November 14, 2021 in South Africa. On November 26, 2021, WHO named the B.1.1.529 Omicron and classified it as a variant of concern because of the number of mutations on the spike protein. As of this yesterday morning (12/8/21), the first Omicron case was reported in Arizona (2). Omicron is also present in California, Utah and Colorado and probably several other states since there is a lag between the presence of the virus and detection.

Early reports have suggested the Omicron variant might cause milder disease more often in children, raising hopes that the variant might be less severe than some of its predecessors (3). Dr. Müge Çevik, an infectious-disease specialist at the University of St Andrews, UK cautions, “Everyone is trying to find some data that could guide us but it’s very difficult at the moment.”

Symptoms

People with COVID-19 have had a wide range of symptoms reported – from none to severe illness (2). Symptoms may appear 2-14 days after exposure to the virus. Symptoms of flu and COVID-19 may be very similar and it may be hard to tell the difference between them based on symptoms alone. Testing may be needed to help confirm a diagnosis. COVID-19 seems to spread more easily than flu and causes more serious illnesses in some people. It can also take longer before people show symptoms and people can be contagious for longer. Despite mild symptoms, people infected with COVID-19 can still infect others.

Testing

Two types of viral tests are used: nucleic acid amplification tests and antigen tests (2). A viral test checks specimens from the nose or mouth by first reverse transcribing the RNA to DNA and then amplifying the DNA by polymerase chain reaction. COVID-19 antigen tests are designed for the rapid diagnosis of active infection primarily by detecting the nucleocapsid protein antigen of the SARS-CoV-2 virus. People who develop symptoms or have come into close contact with someone with COVID-19 should be tested 5–7 days after their last exposure or immediately if symptoms develop.

Prevention

The CDC recommends several steps for prevention of COVID-19 (2).

1. Get Vaccinated. COVID-19 vaccines are protective against COVID-19, especially severe disease and death. Boosters should be administered as soon as possible.
2. Wear a mask. Everyone 2 years or older who is not fully vaccinated should wear a mask in indoor public places. In general, masks are unnecessary in outdoor settings.
3. However, in areas with high numbers of COVID-19 cases, consideration should be given to wearing a mask in crowded outdoor settings and for activities with close contact with others who are not fully vaccinated.
4. Stay 6 feet away from others. Whenever possible, people should stay 6 feet away from others especially those who are sick. If possible, patients should be advised to maintain 6 feet between sick family members.
5. Avoid crowds and poorly ventilated spaces. Crowded places like restaurants, bars, fitness centers, or movie theaters are high risk areas for spread of COVID-19. Indoor spaces that do not offer fresh air from the outdoors should be avoided.
6. Test to prevent spread to others. Testing provides information about the risk of spreading COVID-19. Over-the-counter self-tests can be used at home or anywhere, are easy to use, and produce rapid results.
7. Wash Hands Often. Hands should be washed often with soap and water after the patient blows their nose, coughs, sneezes, or is exposed to any public place.
8. Clean and disinfect. High touch surfaces should be cleaned and disinfected regularly or as needed. This includes tables, doorknobs, light switches, countertops, handles, desks, phones, keyboards, toilets, faucets, and sinks.

Specific Groups

Any immunocompromised group or group living in close contact is at increased risk for COVID-19 infection and complications of the infection (2). This includes asthma, pregnancy, the elderly (>65 years), nearly all chronic diseases and jails or prisons.

Holidays

With Holiday gatherings here, many are concerned about COVID-19 especially with an unvaccinated relative or guest. First, the CDC recommends they get vaccinated (2). Second follow the recommendations under prevention above.

COVID-19 Patients

Patients with COVID-19, should follow the steps under prevention above (2). In addition, they stay home for 10 days after symptoms appear except to get medical care. Patients should be advised to drink fluids, take over-the-counter medications for symptomatic relief, and go to the emergency room or a physician’s office if needed, but call ahead. They should tell their close contacts that they may have been exposed to COVID-19.

COVID-19 Exposure

Patients should quarantine if you have been in close contact (within 6 feet of someone for a cumulative total of 15 minutes or more over a 24-hour period) with someone who has COVID-19, unless they are fully vaccinated (2). People who are fully vaccinated do not need to quarantine after contact with someone who had COVID-19 unless they have symptoms.

Travel

At this time patients should delay travel by bus, train, plane or ship unless fully vaccinated.

Treatment

The NIH has convened a COVID-19 Treatment Guidelines Panel (4). They recommend*:

1. COVID-19 vaccination for everyone who is eligible according to the Advisory Committee on Immunization Practices (AI).
2. Using one of the following anti-SARS-CoV-2 monoclonal antibodies (as post-exposure prophylaxis (PEP) for people who are at high risk of progressing to severe COVID-19:
   • Bamlanivimab 700 mg plus etesevimab 1,400 mg administered as an intravenous (IV) infusion (BIII).
   • Casirivimab 600 mg plus imdevimab 600 mg administered as subcutaneous injections (AI) or an IV infusion (BIII).
3. Do not use hydroxychloroquine for SARS-CoV-2 PEP (AI).
4. Do not use of other drugs for SARS-CoV-2 PEP, except in a clinical trial (AIII).
5. Do not use any drugs for SARS-CoV-2 pre-exposure prophylaxis, except in a clinical trial (AIII).

*Rating of Recommendations: A = Strong; B = Moderate; C = Optional Rating of Evidence: I = One or more randomized trials without major limitations; IIa = Other randomized trials or subgroup analyses of randomized trials; IIb = Nonrandomized trials or observational cohort studies; III = Expert opinion

References

1. Yang H, Rao Z. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nat Rev Microbiol. 2021 Nov;19(11):685-700. [CrossRef] [PubMed]
2. CDC. COVID-19. Available at: https://www.cdc.gov/coronavirus/2019-ncov/index.html (accessed 12-6-21).
3. Callaway E, Ledford H. How bad is Omicron? What scientists know so far. Nature. 2021 Dec 2. [CrossRef] [PubMed]
4. NIH. COVID-19 Treatment Guidelines. October 27, 2021. Available at: https://www.covid19treatmentguidelines.nih.gov/ (accessed 12/6/21).

Cite as: Robbins RA, Klotz SA. A Summary of Outpatient Recommendations for COVID-19 Patients and Providers December 9, 2021. Southwest J Pulm Crit Care. 2021;23(6):151-5. doi: https://doi.org/10.13175/swjpcc066-21 PDF 

December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 56-year-old man was referred for a second opinion on recent onset of diffuse parenchymal lung disease.  He had started noting mild dyspnea with yard work approximately in March 2021. His symptoms progressed over the next month with increasing shortness of breath and some fever. He presented to outside emergency department on April 17, 2021 and chest CT showing patchy ground-glass opacities with some areas of irregular consolidation (Figure 1).

Figure 1. Representative images from the thoracic CT in lung windows from outside emergency room visit.

He was subsequently seen by an outside pulmonologist and started empirically on prednisone (50 mg/day). An outside lung biopsy had been performed which showed nonspecific interstitial pneumonitis. There was some improvement in his symptoms and his prednisone dose was reduced to 20 mg/day; however, his symptoms subsequently worsened with saturations noted to drop to 85% with any ambulation. He also had swelling of his left face and a biopsy of the parotid gland with the findings suggestive of malignancy, possibly melanoma.

What should be done at this time? (Click on the correct answer to be directed to the second of seven pages)

1. History and physical examination
2. Repeat the open lung biopsy
3. Repeat the parotid biopsy
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. December 2021 Pulmonary Case of the Month: Interstitial Lung Disease with Red Knuckles. Southwest J Pulm Crit Care. 2021;23(6):144-8. doi: https://doi.org/10.13175/swjpcc063-21 PDF 

Alveolopleural Fistula In COVID-19 Treated with Bronchoscopic Occlusion with a Swan-Ganz Catheter

Nathaniel Hitt DO¹

Aleksey Tagintsev DO¹

Douglas Summerfield MD¹

Evan Schmitz MD² 

¹MercyOne North Iowa Medical Center, Des Moines, IA USA

²Airod Medical, Gainesville, FL USA

Abstract

Pneumothorax and pneumomediastinum are known complications of COVID-19 patients. They have been documented to occur both with and without mechanical ventilation. There are several reports of cases further complicated by alveolopleural or bronchopleural fistulas. However, there are no studies and only a few case reports on the treatment options used for alveolopleural fistulas in COVID-19 patients. To our knowledge, there is only one report of bronchoscopic treatment with endobronchial valves in a COVID-19 patient. We present the case of a 63-year-old male with COVID-19, pneumothorax, and an alveolopleural fistula that was successfully sealed using bronchoscopic occlusion with a Swan-Ganz catheter.

Abbreviation List

• COVID-19: Severe acute respiratory distress syndrome coronavirus-2
• PAL: Persistent air leak
• APF: Alveolopleural fistula
• PaO2: Partial pressure of arterial oxygen
• FiO2: Fraction of inspired oxygen

Background

Pneumothorax complicates 1% of COVID-19 hospital admissions and the risk increases with mechanical ventilation (1). There have been several reports of pneumothoraces in COVID-19 complicated by persistent air leaks (PAL) and alveolopleural fistulas (APFs) (1-3). APFs are a communication between the pulmonary parenchyma of the alveoli and the pleural cavity. The most common cause is lung reduction surgery, but it can also be present following spontaneous pneumothorax.  Less commonly it can be caused by pulmonary infection. Clinically, APFs present as a PAL on chest tube drainage with a PAL defined as a duration greater than 5 days. Complications include pleural infection and ventilation/perfusion mismatch with a loss of positive end expiratory pressure.  APFs in non-COVID patients have been associated with an increased duration of chest tube, prolonged hospital stay, and increased morbidity a drainage and mortality. Treatments in non-COVID patients have ranged from insertion of additional thoracostomy tubes, surgical intervention, and bronchoscopic intervention (2). There is one reported case of an APF in COVID-19 successfully treated with endobronchial valves (3). Here we present the case of an APF in COVID-19 treated with bronchoscopic occlusion with a Swan-Ganz catheter.

Case Presentation

The patient was a 63-year-old man diagnosed with COVID-19 who required intubation, mechanical ventilation, and admission to the critical care unit. On hospital day 2 chest x-ray revealed bilateral pneumothoraces requiring chest tube placement. Bilateral PAL was present and on hospital day 10 the patient developed a moderate sized right sided pneumothorax despite the adequately positioned chest tube. The initial thoracostomy tube was replaced with a large bore chest tube with immediate resolution of the pneumothorax. However, a moderate air leak persisted and by hospital day 14, the diagnosis of APF was suspected. Bronchoscopic occlusion using the balloon of a Swan-Ganz catheter was performed.

A Swan-Ganz catheter was inserted through the endotracheal tube and along-side of a bronchoscope. The balloon was sequentially inflated and deflated to occlude each lobe to assess for air leak resolution. The air leak was reduced, but not resolved with occlusion of the right lower lobe and right middle lobe individually. The balloon was inflated just enough to occlude the right bronchus intermedius with near complete resolution of the leak (Figure 1).

Figure 1. Chest radiograph showing Swan-Ganz catheter (yellow arrow) with its cuff inflated in the right bronchus intermedius to seal an alveolopleural fistula.

The patient was observed for ten minutes to ensure tolerability before concluding the procedure. He was kept paralyzed to reduce coughing. After 3 days the air leak resolved, the Swan-Ganz catheter was removed, and the air leak remained sealed. The PaO2:FiO2 ratio improved from 79 to 250. However, despite initial improvement and no air leak the patient's conditioned worsened in the setting of multisystem organ failure. Multisystem organ failure was attributed to a combination of severe acute respiratory distress syndrome, cytokine storm, and septic shock from a urinary tract infection. The patient's family made the decision to withdraw care on day 22.

Discussion

Despite several cases of refractory pneumothorax in COVID-19, the significance and optimal treatment remains unclear (1,3,4). There is one report of two COVID-19 patients treated with thoracoscopy, bleb resection, and pleurectomy(4) and a single report of endobronchial valves (3). Conservative management with prolonged chest tube remains the recommended treatment (2). The American College of Chest Physicians guidelines only recommend bronchoscopic treatment in refractory cases when surgery is not possible (2). This patient was not a surgical candidate due to his instability, endobronchial valves were unavailable at our facility, and at height of the COVID-19 pandemic, transfer to a tertiary care center was not possible. Bronchoscopic occlusion with a balloon catheter has been described previously in a case a of PAL secondary to polymicrobial pneumonia, pulmonary interstitial emphysema, and in a case of necrotic lung complicated by hydropneumothorax (2,5,6). Bronchoscopy in COVID-19 is associated with an increased risk of infection and its use should be limited if possible. In this case, it was determined that with proper personal protective equipment and lack of access to other treatments, bronchoscopic occlusion was the best option.

An 8.0 French Swan-Ganz catheter was selected for its balloon that connects to an integrated stopcock to maintain inflation and for its relative availability. We classified the PAL as an APF after the leak was revealed to be distal to the segmental bronchi. The average time to resolution is reported to be 4-7.5 days (2). The decision to maintain occlusion for 3 days was based on the above average, patient improvement, and the lack of drainage from the occluded lung. The risk of infection, in particular pneumonia and empyema, must be considered when using this technique.  Ideally, an endobronchial valve would have been available to allow a one-way valve to drain secretions (2). Our patient was closely monitored for developing pulmonary infection with daily chest radiography and, following the removal of the Swan-Ganz Catheter, a bacterial sputum culture which was negative.

Conclusion

There are no randomized controlled trials investigating which treatment of PALs is most effective or safe in COVID-19 patients or even in non-COVID-19 patients (2). Furthermore, pneumothorax and persistent air leaks in COVID-19 patients have not been universally shown to increase mortality (1). However, considering the known morbidity and mortality associated with PALs, we suggest it may be reasonable in cases refractory to thoracostomy tube to treat with a Swan-Ganz catheter when otherresources are not available.

Acknowledgement

Peter L. Larsen PhD for editorial and administrative support.

References

1. Martinelli AW, Ingle T, Newman J, et al. COVID-19 and pneumothorax: a multicentre retrospective case series. Eur Respir J. 2020 Nov 19;56(5):2002697. [CrossRef] [PubMed]
2. Sakata KK, Reisenauer JS, Kern RM, Mullon JJ. Persistent air leak - review. Respir Med. 2018 Apr;137:213-218. [CrossRef] [PubMed]
3. Pathak V, Waite J, Chalise SN. Use of endobronchial valve to treat COVID-19 adult respiratory distress syndrome-related alveolopleural fistula. Lung India. 2021 Mar;38(Supplement):S69-S71. [CrossRef] [PubMed]
4. Aiolfi A, Biraghi T, Montisci A, et al. Management of Persistent Pneumothorax With Thoracoscopy and Bleb Resection in COVID-19 Patients. Ann Thorac Surg. 2020 Nov;110(5):e413-e415. [CrossRef] [PubMed]
5. Ellis JH, Sequeira FW, Weber TR, Eigen H, Fitzgerald JF. Balloon catheter occlusion of bronchopleural fistulae. AJR Am J Roentgenol. 1982 Jan;138(1):157-9. [CrossRef] [PubMed]
6. Schmitz ED. A new interventional bronchoscopy technique for the treatment of bronchopleural fistula. Southwest J Pulm Crit Care. 2017;15(4):174-8. [CrossRef]

Cite as: Hitt N, Tagintsev A, Summerfield D, Schmitz E. Alveolopleural Fistula In COVID-19 Treated with Bronchoscopic Occlusion with a Swan-Ganz Catheter. Southwest J Pulm Crit Care. 2021;23(4):100-3. doi: https://doi.org/10.13175/swjpcc026-21 PDF