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The effect of cocaine on the nasal cavity and its differential diagnoses looking at three individual cases

Edmiston R

Department of ENT, Wrightington Wigan and Leigh NHS foundation trust, UK

Anmolsingh R

Department of ENT, Wrightington Wigan and Leigh NHS foundation trust, UK

Yu A

Department of ENT, Wrightington Wigan and Leigh NHS foundation trust, UK

Chelliah G

Department of Rheumatology, Wrightington Wigan and Leigh NHS foundation trust, UK

Chitale S

Department of Rheumatology, Wrightington Wigan and Leigh NHS foundation trust, UK

Kumar N

Department of ENT, Wrightington Wigan and Leigh NHS foundation trust, UK

DOI: 10.15761/OHNS.1000186

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Abstract

Systemic vasculitic conditions can present with sino-nasal symptoms. Due to the immunosuppressive agents used to treat such conditions it is vital that an accurate diagnosis is obtained prior to treatment commencing. We present a series of patients with significant nasal destruction and a diagnostic dilemma between a true vasculitic condition and a pseudovasculitis as a result of cocaine use. We review the investigations that can help to determine a definitive diagnosis, multidisciplinary approach needed and discuss the treatment strategies employed in our patients.

Key words

pseudovasculitis, sino-nasal symptoms, vasculitic

Introduction

Various systemic conditions including autoimmune, granulomatous, neoplastic, infective diseases as well as substance abuse can present with sino-nasal manifestations [1]. Due to the complexity of overlapping features, an accurate and prompt diagnosis poses a significant challenge for clinicians.

One particular area of difficulty surrounds the diagnostic uncertainty between a patient with cocaine induced midline destructive lesions (CIMDL’s) and true primary systemic necrotizing vasculitis (PSNV) induced midline destruction. Amongst the subtypes of PSNV, midline lesions occur in up to 90% cases of granulomatosis with polyangitis (GPA) [2]; up to 69% in Eosinophilic granulomatous polyangitis (eGPA) [3] and up to 30% microscopic polyarteritis (MPA) found in [4].

Antineutrophil cytoplasmic antibodies (ANCA) play an important but cumulative role in assisting the diagnosis; along with clinical presentation, imaging, urine analysis and histology. Vasculitides can often demonstrate different patterns of ANCA positivity. GPA is associated with a positive C-ANCA pattern/PR3 antigen with MPA and EGPA being associated with P-ANCA/MPO antigen. Using the combined ANCA and associated target a sensitivity of 85.5% and specificity of 98.6% [5] can be achieved. The time to seroconvert can lead to confusion since many patients with GPA may have false negative levels for some time, despite having a significant sensitivity and specificity.

The presentation of pseudovasculitis, as a result of cocaine abuse, can be ubiquitous in both clinical findings as well as very similar serologicial results (positive ANCA levels) and a bewilderingly similar histological pattern. It is essential that an accurate diagnosis is made to prevent unnecessary exposure to immunosuppressants and also enable key decisions on management.

Methods

We present a series of three cases with a confirmed diagnosis of CIMDL. Data was collected from patient notes and online records. All three patients underwent the same investigative and management approach:

Step 1: Exclude systemic vasculitis

  1. Refer to rheumatology
  2. Urinalysis
  3. Bloods
    1. FBC, ESR, ANCA, Connective tissue screen, ACE, HIV, syphilis

Step 2: Determine extent of disease

  1. CT Sinus / CT Head and neck / CT thorax

Step 3: Restore some healthy nasal mucosa

  1. Saline + lubrication

Step 4: Consider associated problems

  1. Hearing aid referral
  2. Speech and swallowing: Maxillofacial surgeon assessment

Ethical considerations

Patient confidentiality was maintained throughout the review by anonymizing data

Results

Patient one

A 50yr old female was referred to the ENT department with nasal regurgitation; significantly hyponasal speech and a bilateral deterioration in her hearing

Oropharyngeal inspection revealed a 3cm fistula to the right of midline arising from lateral to the incisive foramen anteriorly. Anterior rhinoscopy revealed an absent cartilaginous septum and partially eroded bony septum. The floor of the nose was found to be eroded bilaterally with only a thin layer of mucosa and the lack of visible normal lateral wall architecture. Significant crusting was present, but the post nasal space mucosa was healthy.

On further questioning she admitted to a two-year history of heavy cocaine abuse; having last used cocaine 18 months previously. She also confirmed ‘aggressive’ picking of her nose including using cotton wool buds to remove crusts from deep within her nasal cavity.

Patient two

A 41yr old male patient presented to the maxillofacial department with a 4-week history of oral pain and difficulty in speaking. Examination findings included a granulating septal perforation and fistula of the soft palate. On further questioning he also reported a new history of bilateral hearing loss and a 6-month history of sinusitis like symptoms with nasal obstruction and discharge; managed in the community with numerous courses of oral antibiotics. He had no significant past medical or surgical history but admitted to a four-year history of cocaine use intranasally.

Clinical examination revealed a large septal perforation with a single nasal cavity. Significant crusting was identified within the nasal cavity with ulceration involving destruction of the turbinates.

Patient three

A 24yr old male presented to the respiratory physicians with a 3-year history of increasing shortness of breath and a single episode of haemoptysis. Further questioning revealed a long-standing history of nasal congestion, epistaxis and frontal headaches as well as a history of cocaine abuse having stopped 2 years previously.

Clinical examination revealed a saddle shaped deformity of the nasal bridge with a large septal perforation but a relatively healthy mucosal lining.

Investigation results

Table 1 summarizes the key laboratory investigative findings for the three patients. Importantly, all patients were found to have a mildly raised ANCA with PR3 positive, but no evidence of systemic vasculitis was identified. Follow-up investigations (Table 2) revealed no evidence of systemic involvement with normal renal function and urinalysis. Table 3 demonstrates that significant destruction was seen in 2/3 of the patients CT imaging.

Table 1. Blood test results

Blood tests

Case one

Case two

Case three

Normal ranges

FBC

Hb 124

Hb 95

Hb 164

115-165

ESR

29

68

3

0-27

ANCA (IU/ml)

MPO < 0.2

PR3 3.8

MPO < 0.4

PR3 4.5

MPO 0.9

PR3 11

< 0.9

< 0.9

DsDNA, Centromere B, SS-A, SS-B, Sm, SmRNP, SCL-70, Jo-1, Ribosomal P, Chromatin

Negative

Negative

Negative

 

RF

Negative

Negative

 

 

ACE

Negative

Negative

 

 

TPHA

Negative

Negative

 

 

HIV

Negative

Negative

 

 

Table 2. Follow up investigations

Follow-up investigations

Case one

Case two

Case three

URINAYSIS

Normal

Normal

Normal

U+E

Normal

Normal

Normal

Biopsy

Not performed

Nonspecific changes consistent with vasculitis

Bronchial washings performed: No granulomas or overt necrotic material seen

Table 3. CT sinus reports

Case one

CT SINUS

Absence of hard palate with evidence of fistula between oropharynx and nasal cavity. Absent right middle turbinate and nasal septum. Erosion of medial pterygoid plate.

Maxillary and ethmoid sinus mucosal thickening.

Case two

CT SINUS

Extensive destruction in the paranasal sinuses with destruction of the hard palate on the left and fluid in bilateral mastoid air cells / middle ear clefts with dilatation of the left ICA in the cavernous sinus.

Case Three

CT Head and neck

CT Thorax

No overt signs of systemic vasculitis seen

(No CT sinus performed)

Discussion

Key findings

A diagnostic dilemma arises when a patient with known substance abuse presents to clinic with significant nasal destruction and the clinician has to be able to exclude a systemic vasculitic condition the unfortunate sequalae being that a multisystem disease can go undiagnosed. Early diagnosis of such conditions is key as advanced disease limits the potential benefit of therapy [6].

Cocaine itself is well recognized for its vasoconstrictive properties resulting in localized necrosis of tissues. The vasculitic response seen in CIMDL’s is hypothesized to be a response from the cocaine but increasing evidence has identified levamisole adulterated cocaine to be more toxic in this way and is the main trigger to the vasculitic process. Crew identified that 50% of UK cocaine is cut with levamisole [7] - a synthetic imidazothiazole with immunomodulatory properties. When used in sufficient quantities, it can result in the localized tissue destruction seen with CIMDL’s and also systemic vasculitis and agranulocytosis [8].

Our three cases aid in identifying key differences in presentation, serology and imaging which can help to differentiate CIMDL’s from true vasculitidies. Table 4 provides a comparison between the vasculitic processes that can help with this diagnostic uncertainty looking at histology, serology and systemic involvement.

Table 4. Diagnostic features of ANCA associated vasculitidies

 

MPA

Microscopic polyangitis

GPA

Granulomatosis with polyangitis

eGPA

Eosinophilic granulomatosis with polangitis

Cocaine induced vasculitis

Vessel size

Predominantly small vessel

Predominately small vessel

Predominatly small to medium vessels

Small vessel

Serology

 

P-ANCA/MPO antigen

C-ANCA pattern/PR3 antigen

P-ANCA/MPO antigen

C-ANCA pattern/PR3 antigen (50% cases)

P-ANCA/MPO antigen (almost 100%) [9]

Histology findings [10]

Necrotizing arteritis, glomerulonephritis and capillaritis common.

Granulomatous inflammation absent.

Necrotizing granulomatous inflammation of upper and lower respiratory tract.

Necrotizing glomerulonephritis, pulmonary hemorrhage and ocular vasculitis

Necrotizing granulomatous inflammation – eosinophil rich

Leukocytoclastic vasculitis

Systemic involvement

Common

Common

Asthma

Rare

A key aspect of this is the requirement for histology. In 2016, the European League Against Rheumatism produced consensus statements providing guidance on the management of AAV patients [11] including discussions over the role of performing biopsies. In this study, they explain that a positive biopsy is strongly supportive of a diagnosis and biopsies are recommended to assist in establishing a new diagnosis. The important element to consider is the location from which they are taken. In GPA patients with renal involvement, diagnostic yield from renal biopsy can be as high as 91.5% and biopsies of nasal mucosa may be positive for inflammatory changes in 68.4%. A large study looking at diagnostic yield from ENT biopsies revealed that they are often positive for non-specific chronic inflammation and it is significantly less common to find granulomas and vasculitis when compared to lung and kidney biopsies [12].

The implication of such a low diagnostic yield has led to our conclusion that nasal biopsies should not be part of routine practice (as demonstrated within our cases series). The exception to this is in the presence of very abnormal looking mucosa where other differential diagnoses are being considered such as lymphoma.

Treatment strategies

All three patients were managed by the same rheumatology, maxillofacial and ENT teams with short term oral steroids and abstinence from cocaine use.

Though the literature search is limited, we have found that a moderate dose of steroids normally 60-80 mg on a reducing regime over 3 to 6 months works well as an immunomodulator to halt the vasculitic process. Very few patients, as described above, need steroid sparing agents (such as Azathiaprine). However, if a systemic vasculitic process has been identified, this would have been the next management step. Case one and two had significant palatal destruction requiring temporary management with an obturator and are both planed for reconstructive surgery with a radial forearm free flap when the mucosa is more healthy.

Clinical applicability

In summary we have identified that there are certain features that can aid in confirming a diagnosis of CIMDLs over other causes:

  • CT scans often demonstrate soft tissue thickening of nasopharynx, soft palate and oropharynx with bony destruction of palate, lateral nasal wall, turbinates, septum and ethmoid sinuses [13].
  • Biopsy should only be done to exclude malignancy where abnormal mucosa is seen.
  • Serological markers can improve diagnostic yield with up to 56% c-ANCA positive with CIMDL [14] and more often very high titres of MPO ANCA antibodies [15].
  • Once the diagnosis is confirmed, such patients must be managed by a multidisciplinary team:
  • ENT surgeons are required to consider the potential of a systemic vasculitic condition, manage the nasal mucosa and aid in performing biopsies when needed.
  • Rheumatologists can help with the diagnostic dilemma and also given advice on the management of such localized vasculitis as well as manage any associated systemic involvement.
  • Maxillofacial teams can facilitate both temporary and long-term management of the extensive destruction that may occur.

Key points

  1. CIMDLs to this extent are rare but it is important that we make an accurate diagnosis since the differential diagnosis is PSNV which needs an aggressive management plan.
  2. Patients with confirmed vasculitis should be managed by specialist teams in a multidisciplinary approach with CIMDLs requiring input from ENT, Maxillofacial, rheumatology as well as allied teams such as audiology.
  3. The diagnosis can be difficult, but clinicians should always enquire about cocaine use in the patient history. Diagnostic features that help to confirm a CIMDL rather than primary vasculitis include characterized destructive changes on CT, but clinicians must be aware of the overlap in serology and histological features.

References

  1. Fuchs HA, Tanner SB (2009) Granulomatous disorders of the nose and paranasal sinuses. Curr Opin Otolaryngol Head Neck Surg 17: 23-27. [Crossref]
  2. Falk RJ, Gross WL, Guillevin L, Hoffman GS, Jayne DR, et al. (2011) Granulomatosis with polyangiitis (Wegener's): An alternative name for Wegener's granulomatosis. Arthritis Rheum 63: 863-864. [Crossref]
  3. Pagnoux C, Wolter NE (2012) Vasculitis of the upper airways. Swiss Med Wkly 142: w13541. [Crossref]
  4. Olsen KD, Neel HB III, Deremee RA, Weiland LH (1980) Nasal manifestations of allergic granulomatosis and angiitis (Churg-Strauss syndrome). Otolaryngol Head Neck Surg 88: 85-89. [Crossref]
  5. Choi HK, Liu S, Merkel PA, Colditz GA, Niles JL (2001) Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase antibodies. J Rheumatol 28: 1584-1590. [Crossref]
  6. Lapraik C, Watts R, Bacon P, Carruthers D, Chakravarty K, et al. (2007) BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology (Oxford) 46: 1615-1616. [Crossref]
  7. http://www.erowid.ord/cocaine/cocaine_article2.shtml
  8. Graf J, Lynch K, Yeh C, Tarter L, Richman N, et al. (2011) Purpura, cutaneous necrosis and antineutrophil cytoplasmic antibodies associated with levamisole adulterated cocaine. Arthritis rheum 63: 3998-4001. [Crossref]
  9. Yates M, Watts R, Bajema I, Cid M, Crentani B, et al. (2016) EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 75: 1583-1594. [Crossref]
  10. Devaney KO, Travis WD, Hoffman G, Leavitt R, Lebovics R, et al. (1990) Interpretation of head and neck biopsies in Wegener's granulomatosis. A pathologic study of 126 biopsies in 70 patients. Am J Surg Pathol 14: 555-564. [Crossref]
  11. Diamantopoulos II, Jones NS (2001) The investigation of nasal septal perforations and ulcers. J Laryngol Otol 115: 541-544. [Crossref]
  12. Trimarchi M, Nicolai P, Lombardi D, Facchetti F, Morassi ML, et al. (2003) Sinonasal osteocartilaginous necrosis in cocaine abusers: Experience in 25 patients. Am J Rhinol 17: 33-43. [Crossref]
  13. Choi HK, Merkel PA, Walker AM, Niles JL (2000) Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies. Arthritis Rheum 43: 405-413. [Crossref]
  14. Abdul-Karim R, Ryan C, Rangel C, Emmett M (2013) Levamisole-induced vasculitis. Proc (Bayl Univ Med Cent) 26: 163-165. [Crossref]
  15. McKinney E, Willcocks L, Smith C (2014) The immunopathology of ANCA- associated vasculitis. Semin Immunopathol 36: 461-478. [Crossref]

Editorial Information

Editor-in-Chief

Chin-Lung Kuo
Taoyuan Armed Forces General Hospital

Article Type

Case Report

Publication history

Received date: September 05, 2018
Accepted date: September 21, 2018
Published date: September 25, 2018

Copyright

© 2018 Edmiston R. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Edmiston R, Anmolsingh R, Yu A, Chelliah G, Chitale S, et al. (2018) The effect of cocaine on the nasal cavity and its differential diagnoses looking at three individual cases. Otorhinolaryngol Head Neck Surg 3: DOI: 10.15761/OHNS.1000186

Corresponding author

Edmiston R

Department of ENT, Wrightington Wigan and Leigh NHS foundation trust UK

E-mail : bhuvaneswari.bibleraaj@uhsm.nhs.uk

Table 1. Blood test results

Blood tests

Case one

Case two

Case three

Normal ranges

FBC

Hb 124

Hb 95

Hb 164

115-165

ESR

29

68

3

0-27

ANCA (IU/ml)

MPO < 0.2

PR3 3.8

MPO < 0.4

PR3 4.5

MPO 0.9

PR3 11

< 0.9

< 0.9

DsDNA, Centromere B, SS-A, SS-B, Sm, SmRNP, SCL-70, Jo-1, Ribosomal P, Chromatin

Negative

Negative

Negative

 

RF

Negative

Negative

 

 

ACE

Negative

Negative

 

 

TPHA

Negative

Negative

 

 

HIV

Negative

Negative

 

 

Table 2. Follow up investigations

Follow-up investigations

Case one

Case two

Case three

URINAYSIS

Normal

Normal

Normal

U+E

Normal

Normal

Normal

Biopsy

Not performed

Nonspecific changes consistent with vasculitis

Bronchial washings performed: No granulomas or overt necrotic material seen

Table 3. CT sinus reports

Case one

CT SINUS

Absence of hard palate with evidence of fistula between oropharynx and nasal cavity. Absent right middle turbinate and nasal septum. Erosion of medial pterygoid plate.

Maxillary and ethmoid sinus mucosal thickening.

Case two

CT SINUS

Extensive destruction in the paranasal sinuses with destruction of the hard palate on the left and fluid in bilateral mastoid air cells / middle ear clefts with dilatation of the left ICA in the cavernous sinus.

Case Three

CT Head and neck

CT Thorax

No overt signs of systemic vasculitis seen

(No CT sinus performed)

Table 4. Diagnostic features of ANCA associated vasculitidies

 

MPA

Microscopic polyangitis

GPA

Granulomatosis with polyangitis

eGPA

Eosinophilic granulomatosis with polangitis

Cocaine induced vasculitis

Vessel size

Predominantly small vessel

Predominately small vessel

Predominatly small to medium vessels

Small vessel

Serology

 

P-ANCA/MPO antigen

C-ANCA pattern/PR3 antigen

P-ANCA/MPO antigen

C-ANCA pattern/PR3 antigen (50% cases)

P-ANCA/MPO antigen (almost 100%) [9]

Histology findings [10]

Necrotizing arteritis, glomerulonephritis and capillaritis common.

Granulomatous inflammation absent.

Necrotizing granulomatous inflammation of upper and lower respiratory tract.

Necrotizing glomerulonephritis, pulmonary hemorrhage and ocular vasculitis

Necrotizing granulomatous inflammation – eosinophil rich

Leukocytoclastic vasculitis

Systemic involvement

Common

Common

Asthma

Rare