Clinics in Dermatology (2014) 32, 817–826
Nasal septal ulceration Kabir Sardana, MD, DNB, MNAMS ⁎, Khushbu Goel, MD Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
Abstract Nasal septal ulceration can have multiple etiologies. Determining the exact cause depends on who the consulting specialist is, who could either be the ENT surgeon or the dermatologist. The common causes are infections (tuberculosis, leprosy, leishmaniasis), vasculitis (Wegener’s granulomatosis and Churg-Strauss syndrome), and lupus erythematosus. Traumatic causes and malignancy can also be seen in tertiary referral centers. The diagnosis often requires thorough investigations and multiple tissue specimens from various sites, and in chronic cases, a suspicion of lymphoma should be considered. Apart from disease-specific therapy, a multidisciplinary approach is required in most cases to tackle the cosmetic disfigurement. © 2014 Elsevier Inc. All rights reserved.
Introduction Nasal septal ulceration is defined as deep erosion extending to the mucosa, submucosa, and the perichondrial layers exposing the nasal cartilage. Nasal septal perforation (NSP) represents a complete breach through all layers and the cartilage. These are often a cause of concern, as they may be the first sign of numerous underlying infective, autoimmune, or systemic disorders; or many of them may be idiopathic in nature. Historically, though syphilis has been described as a common cause for affliction of the nose, in dermatologic practice (Table 1), the most common causes are leprosy, lupus vulgaris, DLE, and squamous cell carcinoma. Almost all of the studies conducted on this topic deals with nasal septal ulceration and perforation simultaneously as the latter usually follows the former, so most of the data provided here would encompass both these terms with special mention of nasal septal ulceration as and when possible.
Anatomy and pathogenesis The arterial blood supply of the nose is primarily from the external and internal carotid arteries. The site where ⁎ Corresponding author. Tel.: +919968604369; fax: +9123234648. E-mail address: [email protected]
(Professor K. Sardana). http://dx.doi.org/10.1016/j.clindermatol.2014.02.022 0738-081X/© 2014 Elsevier Inc. All rights reserved.
perforation occurs is at the anterior portion, which is supplied by superior labial artery along with branches from the sphenopalatine and greater palatine artery that feed the Kiesselbach plexus (Little’s area), located on the anterior cartilaginous septum.1 The nasal septal cartilage, which is a relatively avascular area, is covered by the nasal septal mucoperichondrium (mucosal and perichondrial vasculature). Any insult (chemical or physical) that produces damage to the normal anatomy can lead to ischemic necrosis of the septal cartilage, resulting in perforation. Disruptions of the septal mucosa are called erosion or ulceration. Excoriation refers to superficial erosion through the mucosa or submucosa but not through the perichondrial layers. Ulceration is defined as deeper erosion to the perichondrial layers exposing cartilage, whereas NSP represents a complete breach through all layers and the cartilage. If the healing of the NSP is improper, the area is covered by an atrophic layer of mucosa, which leads to crusting and bleeding due to the friction consequent to the disrupted airflow.2 Four well-marked stages are recognized in formation of ulceration and subsequent perforation.3 The first consists of redness and irritation of the mucosa covering the septum, together with rhinorrhoea. This is followed by blanching of the mucosa over the lower, anterior part of the septum, Kiesselbach’s or Little’s area, which is relatively avascular
818 Table 1
K. Sadarna, K. Goel Causes of nasal septal ulceration and perforation
Nasal septal ulceration
Postnasal surgery External trauma
Acute exacerbation of SLE Pyoderma gangrenosum
Pemphigus vulgaris Pemphigoid Behcet’s disease Hydroa vacciniforme b Bacterial cause (Staph aureus) Typhoid Diphtheria Glanders
Self-inflicted a: Nose picking, impacted foreign bodies, Factitial dermatitis DLE a SLE Wegener’s granulomatosis a sarcoidosis (nasopharyngeal mutilation) Churg strauss disease RA Crohn’s disease Eosinophilic angiocentric fibrosis (variant of granuloma faciale) b
Vascular causes Neoplasms
Chemical irritants: Chrome, sulfuric, hydrochloric acids, cyanides, arsenic, chlorines and bromines Physical irritants: Agricultural aerosolized dust, Rice and grain elevator dust, Chemical and industrial dusts, Lime, cement, glass, salt, dust Heavy metal
Congenital disorders are not included in this list. a Common causes. b Causes saddle nose deformity.
Tuberculosis a,b Leprosy a,b Leishmaniasis (mucocutaneous leishmaniasis) a PKDL a Cancrum oris (noma) Deep fungal infections Syphilis (nasal septum) Yaws nasopharyngeal mutilation (gangosa) Rhinosporidiosis AIDS Myiasis Hemangioma (Cyarano Nose defect) Lethal midline granuloma (LMG)-nasal natural killer (NK) T-cell lymphoma (LMG-NTL) a Adenocarcinoma Basal cell carcinoma Chondrosarcoma Malignant epithelial and mesenchymal tumors (sarcomas) Malignant histiocytosis Squamous cell carcinoma Metastatic carcinoma B-cell lymphoma Leukemia Illicit drug use: Cocaine a Nasal sprays (steroids) Trigeminal trophic syndrome (Wallenberg’s syndrome)
Anhidrotic ectodermal dysplasia b APLAS (nasal tip necrosis) Hurlers syndrome b Hyper IgE syndrome Porphyria – congenital erythropoietic porphyria Relapsing polychondritis b Prolidase deficiency
Fig. 2 Patient with DLE with involvement of the bridge of the nose, which if untreated can lead to ulceration of the nasal septum.
Fig. 1 Post-traumatic destruction of the nasal septum resulting in collapse of the bridge of nose leading to the “saddle nose “deformity.
and closely adherent to the underlying cartilage. Extensive crusting occurs over the affected area, leading to discomfort and consequent nose picking, which carries the risk of abrasion and further contamination of the affected area. Ulceration at the site occurs, which leads to perforation of the septum within 1 or 2 weeks. The perforation may increase in size, extending upwards and posteriorly. During this stage of active ulceration, slight bleeding from the nose and pain at the bridge of the nose, particularly on contact with cold air, are common complaints. If there is no additional insult, within 3 months, the edges of the perforation heal with the formation of avascular scar tissue.
Epidemiology Though there is a paucity of studies on the prevalence or incidence of nasal septal ulceration and perforation, a major study has found it to be less than 1% in healthy population in Scandinavians4 while another study found it to be as high as 35% in workers of electroplating factories5. Another study had 74 patients with nasal septal ulceration and NSP of which 54 had perforation and 20 had ulcer.6 The sex ratio was equal, and mean age of presentation was 54 years (range: 14-88).
far the most common symptom being reported in 53% of patient in one series7 and 43% in another.6 Rhinorrhoea and hyposmia may also be seen in some patients. Approximately 15% of the patients may be totally asymptomatic with lesions being detected on routine examination. On examination, crusting with minor bleeding points is the most common finding on anterior rhinoscopy.6 NSP in addition may present with whistling and turbulence that further leads to dryness, rhinorrhoea, crusting, and subsequently to obstruction. Patient with NSP may also present with headache or voice change.
Location In a study of 74 cases, it was found that 92% of NSPs and ulcerations were seen anteriorly and 8% were located posteriorly or superiorly.6 The anterior portion is more frequently affected as it is covered by a thin mucosa, lacks cilia, and is more susceptible to inflammation and ischemia leading to epithelial necrosis and chondrolysis. The lesion is considered posterior if it is located 1 cm or more behind the anterior end of inferior turbinate. These posterior lesions are more commonly associated with trauma or systemic disease such as neoplasia, connective tissue disorders, and syphilis, whereas the anterior ones, which are more symptomatic, may be more associated with trauma.
Causes of nasal septal ulceration Clinical presentation The patients with nasal septal ulceration usually present with epistaxis, crusting, obstruction, and pain. Bleeding is by
A study has found that the most common entity (47%) was idiopathic, 39% were traumatic, 8% inflammatory, and 3% were infectious in etiology.6 The various causes are listed in Table 1, and we will focus on the major causes in our review.
K. Sadarna, K. Goel spholipid antibody syndrome, and sarcoidosis. Clinical manifestations are usually nonspecific and include obstruction, epistaxis, post nasal discharge, whistling, and crusting though in many cases this may be asymptomatic. Diagnosis is usually based on presence of other associated features and laboratory tests.
Fig. 3 A case of hypertrophic lupus vulgaris involving the nose and the upper lip with extensive involvement and ulceration of the nasal mucosa (lupus vorax).
Trauma This can be self-inflicted, secondary to various surgical procedures or due to external trauma. Self-inflicted injury is usually a result of nose picking. A study found nose picking as a cause of nasal ulceration in 6/20 patients, consequentially it is more common than believed, though this may not present to dermatologists.6 Various surgical procedures leading to septal perforation include procedures for deviated nasal septum or cautery for epistaxis.8 Tight nasal packs, especially in patients who have had previous septoplasty, may compress the vascular supply to the septum and if left in place long enough can lead to septal perforation, secondary to interruption of mucoperichondral blood supply. Endoscopic sinus surgery, trans-septal approaches to sphenoid and nasal antral window surgery have also been implicated in causes of iatrogenic perforations.9 External trauma to the nose can cause fracture of the septum with the possibility of disruption of the mucoperichondrium with cartilaginous fractures (Figure 1). If fractures with tears are left untreated, infection and perforations can result. An undiagnosed and untreated septal hematoma from trauma can result in fibrosis with loss of the intervening cartilage or can become infected and develop an abscess leading to a perforation.
Systemic diseases Various systemic diseases may be responsible for nasal septal ulceration and perforation like Wegener’s granulomatosis, systemic lupus erythematosus (SLE), antipho-
Systemic lupus erythematosus Mucosal lesions are seen in 9% to 18% of SLE cases, with oral, nasal, and pharyngeal mucosas being most commonly affected.10,11 A study described three patients who had ulceration that developed with the acute exacerbation of SLE.12 The patients responded well to high dose of steroids (60 mg prednisolone), but recurrence was seen in one of the patients. A study reported six SLE patients with asymptomatic anteroinferior nasal septal perforations and hypothesized that nasal septal perforation in SLE is a common phenomenon, and its infrequent detection is due to asymptomatic nature of the lesion in this setting.13 Discoid lupus erythematosus Mucosal lesions occurs in 25% of patients with DLE and nasal lesions are seen in 9% of the cases (Figure 2). The oral mucosa is most frequently affected; however, nasal, conjunctival, and genital mucosal surfaces may also be affected. Perforation of the nasal septum is more often associated with SLE than DLE. Wegener’s granulomatosis It is characterized by necrotizing granulomas with vasculitis of the upper and lower respiratory tract, systemic vasculitis, and focal necrotizing or proliferative glomerulonephritis.14 Rhinologic symptoms include nasal congestion, rhinorrhea, and anosmia, which may further progress to rhinitis, sinusitis, septal ulceration, perforation and/or nasal airway stenosis. Nasal endoscopy typically reveals mucosal cobble stoning, edema, and crusting.15 Nasal septal ulceration and perforation is usually seen in patients with associated widespread systemic symptoms.16 A study reported Wegener’s granulomatosis as a cause of perforation in 6/54 patients.6 Sarcoidosis Lupus pernio is the most characteristic skin lesion of sarcoidosis seen more commonly in women. The frequency of extrapulmonary involvement and the number of patients with advanced stage disease is higher in these patients than in other cutaneous manifestations of sarcoidosis.17 Nasal septal perforation has been described in patients of sarcoidosis by many workers.18,19 Sarcoidosis is a chronic systemic granulomatous disease capable of involving almost any organ in the body. Although involvement of the epithelium of the upper respiratory tract is comparatively infrequent, nasal symptoms may be the first manifestation of
821 the nasal vestibule.25 Wegener’s should be considered as a close differential wherein systemic lesions of granulomatous vasculitis are seen with a positive cytoplasmic antineutrophil cytoplasmic antibody. Nasal lesions of pyoderma gangrenosum have rarely been reported; however, there is a possibility that nasal lesions in pyoderma gangrenosum have been overlooked, because the subjective symptom of nasal septal perforation may be only mild nasal discharge.
Cutaneous disorders leading to nasal ulceration
Fig. 4 Nasal septal perforation with destruction of nasal cartilage in a patient with long-standing leprosy
this disease. The true incidence of nasal involvement is not known with certainty. The most frequent symptom of nasal involvement is nasal obstruction, but epistaxis, dyspnea, nasal pain, epiphora, and anosmia may also occur. Nasal sarcoidosis commonly affects the mucosa of the septum and inferior turbinate.20 Submucosal nodules representative of intramucosal granulomas with a characteristic yellow color may be noted and can be identified in mucosal biopsies. The diagnosis of sarcoidosis of the nose and paranasal sinuses is based on the clinical findings of crusting friable nasal mucosa with either polypoid changes or characteristic yellowish submucosal nodularity. Crohn’s disease Nasal septal ulceration may be a rare manifestation of Crohn’s disease.21 This is a chronic inflammatory bowel disease characterized by discontinuous involvement of the entire alimentary tract, from the mouth to the anus. Nasal disease and septal involvement are quite rare.22 Symptoms of nasal Crohn’s typically include obstruction, rhinorrhea, and epistaxis and examination reveals atrophic rhinitis, chronic mucosal inflammation, and granuloma formation. Mucosal oedema, chronic inflammation, and polypoidal changes involving septum or turbinates may be found.22 Histologic findings are variable and granulomas may or may not be present. Steroids are the mainstay of treatment.
Pemphigus vulgaris is a common mucocutaneous bullous disorder characterized by nonscarring bullous dermatitis of presumed autoimmune origin. The oral cavity is the most common site involved in the head and neck region with about 10% of all patients presenting with involvement of the nasal mucosa. Desquamative ulcerative lesions can be seen and ulceration of the nasal septum with anterior perforation has also been reported.16 Pemphigoid and more commonly cicatricial pemphigoid affects the nasal mucosa in about 25-50% of affected patients.26 The usual site of involvement is the anterior nasal region, which is found to have painful, ulcerative crusting. Scarring may be bilateral and lead to partial or total nasal obstruction. Behcet’s disease is characterized by the triad of oral ulceration, genital ulceration, and ocular inflammation. The typical aphthous ulceration found in the oral cavity in this disease can also be found in the nasal mucosa. These lesions typically heal without scarring but can cause rhinorrhea and pain.
A. Infections causing nasal septal ulceration Tuberculosis The occurrence of extra-pulmonary TB is rising, and now constitutes 40% of the total incidence of the disease, with many cases involving the ear nose and throat.27
Pyoderma gangrenosum Pyoderma gangrenosum is characterized by chronic cutaneous ulcers with well-defined, deep erythematous to violaceous, undermined borders. The lesions most commonly affect the lower legs; while lesions in the head and neck areas are rare.23 Intranasal lesions are rarely reported: A study reported two patients with pyoderma gangrenosum of the legs complicated with nasal septal perforation.24 One report also described an ulcer located on the medial aspect of
Fig. 5 Nasal endoscopic examination of a patient of Trichosporinosis revealing nasal septal perforation.
An overview of selected disorders causing nasal septal ulceration
History and examination
History of photosensitivity, dermatitis, joint pains, oral ulcers, fever
ANA, ds DNA, Hemogram, urinanalysis with 24-hr urinary protein, LE cell, RA factor Abnormal ESR, decreased haemoglobin, Wegener’s granulomatosis Prolonged upper respiratory tract infection, pulmonary involvement with cough, hemoptysis, serum creatinine and c-ANCA. and cavitary lesions on chest X ray. progressive renal involvement Sarcoidosis
Pulmonary involvement, iridocyclitis, anterior uveitis, erythema nodosum, lupus pernio, polyarthralgia, myopathy, enlarged lymph node
Allergic rhinitis, asthma; pneumonia, gastroenteritis, nasal polyps
Chronic cough with sputum, low grade fever, weight loss, h/o TB in family or self in past, lymphadenopathy
Elevated serum or urinary calcium, Increased radiogallium uptake in the nasal mucosa, Increased ACE levels, Abnormal sinus CT, chest X ray and CT: reveals hilar lymphadenopathy/ pulmonary fibrosis Eosinophilia, negative C-ANCA, positive p-ANCA
Microscopy (ZN stain), Mantoux, Chest X ray, Skin biopsy and culture. New techniques: Nucleic acid amplification tests, PCR, interferon γ assay (Note: Nasal secretions and swab have a very low yield on microscopy) ZN and fite stain for lepra bacilli, histopathology is usually diagnostic
GC, Glucocorticoid; CYC, Cyclophosphamide; Mtx, Methotrexate.
Liquefactive degeneration of basal layer, fibrinoid necrosis, collagen sclerosis, perivascular infiltrate Vasculitis of medium and small vessels with intramural eccentric necrotizing granulomatous lesions, typically involving arteries, arterioles, capillaries, venules, and veins Multiple noncaseating granulomas consisting of a central area of tightly packed epitheliod cells surrounded by lymphocytes and fibroblasts. MNG’s are frequently found
High dose oral steroids GC + CYC/Mtx
GC +/- CYC Necrotizing vasculitis of small and medium sized vessels with necrotizing extravascular granulomas and prominent eosinophilia Granuloma with central caseous necrosis. Antitubercular therapy Granuloma consist of giant cells and epithelioid cells
Antileprosy Grenz zone, sheets of macrophages multidrug treatment infiltrating the dermis, very few lymphocytes with occasional plasma cells Abundant hyphal growth with inflammatory reaction, necrotizing abscesses Perivascular infiltrate of plasma cells and lymphocytes, Increased angiogenesis
IV Amphotericin B voraconazole, posaconazole. Injection benzathine penicillin in the active stage
Diffuse infiltration with macrophages filled with amastigotes
K. Sadarna, K. Goel
To be suspected in patients from endemic area, look for features of advanced lepromatous disease with shiny infiltrated skin, ENL, and nerve involvement Fungal infection Immunocompromised patient, extensive destructive Biopsy for histopathology with special stains lesion, evidence of fungal infection elsewhere and culture. CT scan of the sinuses may show a destructive bony lesion VDRL, FTA-abs, TPHA, dark field Syphilis Mucosal involvement is seen in sexually microscopy. active patients, secondary syphilis- dermatitis and lymphadenopathy, Nasal involvement is seen also in congenital syphilis and gummatous stage of syphilis. Leishmaniasis and PKDL Patient is from a endemic area, cutaneous Slit skin smear or tissue smear for lesions are seen with a history of kala azar microscopy, culture of the secretions in in case of PKDL N.N.N. culture medium and K39 ELISA test
Nasal ulceration Mycobacterium tuberculosis (lupus vulgaris): The clinical variant of lupus vulgaris that affects the nose is the vegetative and ulcerative form and the associated destruction of cartilage (lupus vorax) leads to the saddle nose deformity (Figure 3). Lupus vulgaris is probably more common than the primary form or TB cutis orifacialis. Interestingly in endemic areas this is commonly seen by dermatologist than ENT specialist.28,29 Primary nasal tuberculosis is an uncommon condition mainly confined to endemic areas of the world.30,31 It is caused by inhalation of infected particles or traumatic digital inoculation. The nasal septum is more frequently involved than the lateral wall. 31 Symptomatology is often unilateral with nasal obstruction, anterior rhinorrhea, or epistaxis. The clinical examination may discover ulceration or a polyp located generally in the nasal septum or the inferior turbinate. Septal perforation has also been reported with atypical mycobacterial infection caused by mycobacterium kansasii.32 The differential diagnoses include malignancy, Wegener’s granulomatosis, sarcoidosis, syphilis, and fungal infection. Nasal secretions and swab specimens have a very low yield and should not be used to rule out nasal TB.33 For definitive diagnosis, histopathology with culture should be done, along with notification of the types of organism suspected. Though culture and PCR have been touted as the gold standard, we believe a therapeutic challenge for 6 weeks is a valid diagnostic criterion.34
Leprosy Advanced lepromatous leprosy can involve most organs in the body, including structures in the ear, nose, and throat; however, with widespread use of multidrug therapy such manifestations are becoming less common. The nasal mucosa has been shown to be affected by M. leprae35 and probably serves as a portal of entry for infection. The nasal mucosa is involved in 95% of patients with lepromatous leprosy36 and has been found to be affected in all patients with advanced lepromatous disease. Although uncommon, epistaxis may be the first indication that a patient has leprosy and is often a result of nasal blockage, thick discharge, ulceration, and sometimes of septal perforation (Figure 4). This is consequent to the involvement of the arteriovenous complex of the nasal mucosa, exaggerating pre-existing local pathology.37 Bacillary destruction of the bony nasal spine can cause collapse of the nose, leading to the characteristic “saddle-nose” deformity (Figure 4). Nasal myiasis may occur in patients with mucosal ulcers and discharge. If neglected, these larvae may burrow deeply, causing extensive tissue destruction. Nasal or palatal fistulae may occur, and cavernous sinus thrombosis is a potentially fatal complication.38 Nasal deformity can be prevented by the early institution of multidrug therapy. Concomitant lavage for cleansing the
823 nasal cavity and the application of a thin layer of Vaseline or liquid paraffin helps minimize crusting and ulceration.
Fungal infection Fungal sinusitis appears rarely in immunocompromised patients and Aspergillus sp. and Mucor sp. are the most commonly involved fungi. Patients present with bloody nasal discharge, facial pain and swelling, fever, and edema. The disease often progresses rapidly in an invasive manner to cause facial cellulitis, gangrenous mucosal changes in the nose, and paranasal sinuses resulting in nasal septal ulceration and perforation, obtundation, cranial nerve palsies, vision loss, and proptosis.39 Other rare causes can affect the nasal mucosa (Figure 5). Diagnosis is established via physical exam findings of pale or gray mucosa of the nasal cavity or palate or the classic black middle turbinate.40 Decreased pain and sensitivity of the nasal cavity is a suspicious sign.
PKDL Postkala-azar mucosal leishmaniasis (PKML) is relatively rare in the Indian subcontinent. One study described an ulcerative variant of PKML with nasal involvement in a Nepalese adult man.41 He had ulcerated plaque over the upper lip with extensive involvement of nasal columella and septum. There were abundant LD bodies in microsections and FNA of submandibular lymph node. Nasal septal ulceration has also been described in leishmaniasis.42
B. Neoplastic conditions Lethal midline granuloma (LMG)-nasal natural killer T-cell lymphoma (LMG-NTL): LMG is a rare entity that usually arises in the nasal cavity, exhibits a male preponderance, and has a wide age range. The majority of LMGs are LMG-NTLs. T-cell lymphoma usually present with nasal obstruction followed by purulent rhinorrhea and serosanguinous discharge. As symptoms progress, usually unilateral mucosal ulceration with extension into the palate, maxillary sinus, and upper lip may occur. Mucosa is often pale, friable and extensive crusting is often present. Oronasal fistulas as well as nasal septal perforations may occur.43,44 Typically, there is an explosive unilateral involvement of one side of the nose, face, palate, and orbit. The optimal treatment of LMG-NTL is unclear and most likely moderate-dose radiotherapy is an appropriate intervention. The prognosis for patients with LMG-NTL is significantly worse than for patients with other types of head and neck non-Hodgkin lymphomas. The 5-year survival rate is approximately 20% but may be higher, depending on whether patients with less aggressive forms of non-Hodgkin
824 lymphomas are included. Initial local-regional disease progression is the predominant pattern of treatment failure. Late failures after 5 years are uncommon.44 Neoplastic disorders, such as metastatic carcinoma and squamous and adenoid carcinomas and melanomas, must be ruled out in a case of malignant nasal septal ulceration. Leukemia and B-cell lymphomas may also have nasal presentations.16 B-cell lymphomas may cause unilateral nasal obstruction by an enlarged nasal or nasopharyngeal mass. Acute leukemia may produce symptoms of an upper respiratory infection or cause epistaxis secondary to friable mucosa in the anterior nose.
C. Other causes Chemical and chrome ulceration of the nasal septum Ulceration of the skin and nasal septum have been recognized as hazards to persons in occupations involving chrome compounds such as chrome plating, chrome tanning, dyeing and finishing, and the manufacture of bichromates.3 Chrome ulceration results from penetration of the skin or mucous membrane by chromium in the hexavalent form; the trivalent compounds do not give rise to ulceration. Nasal septal ulceration and perforation has also been described in individuals working as jiggers (the workers who prepare the items before plating by attaching items to be plated onto jigs or frames) in the chromium electroplating industry.45 Other causes are exposure to anhydrous sodium carbonate (soda ash); arsenic and its compounds; organic compounds of mercury, particularly mercury fulminate; alkaline dusts, such as soap powders; hydrofluoric acid and fluorides; capsaicin; vanadium; dimethyl sulfate; cocaine and other drugs taken as snuff; copper salts (rarely) and lime (rarely). The habit of nose picking or septal deviation might predispose these patients to ulceration. Because it may be asymptomatic, such patients should undergo routine examination at regular intervals. Sodium calcium edetate ointment has both therapeutic and prophylactic role in nasal septum ulceration.
Illicit drug use Illicit drugs, particularly cocaine, have been associated with NSP. Cocaine not only causes vasoconstriction by inhibition of noradrenalin reuptake, but also competes with calcium ions and controls the flux of sodium ions. This inhibition stops the generation of nerve impulses and produces local anesthesia so the user does not feel pain and trauma when inserting spoons and other objects into the nose.2 Also, illegal suppliers extend or “cut” cocaine with known irritants such as borax and talcum powder. These adulterants may contribute to the mucosal destruction. Chronic cocaine abusers in conjunction with infection worsens the condition to such an extent that membrane, bone, and cartilage necrosis takes place and leads
K. Sadarna, K. Goel to perforation, nasal collapse, intranasal stenosis, and saddling. Chronic cocaine abusers usually are easy to detect in the office, based on their jittery habits, their wired, intense appearance, and their chronic nasal sniffing.9
Nasal sprays One study noted that chronic use of nasal sprays may lead to septal perforations.46 These are used for rhinorrhea, and the vasoconstrictive sprays can affect the mucoperichondrium and can lead to perforations. Initial epistaxis seen early in the use of any nasal spray may be largely due to a mechanical trauma from touching or abrading the nasal septum with the hard plastic tip of the applicator, which may lead to erosions and sometimes even ulcerations.2 The advent of the steroid nasal sprays and the rise of their long-term use have increased the risk of septal perforation and so patients on these medications should be monitored periodically.
Chemical irritants Industrial and agricultural aerosolized dust, as found in grain and rice elevators and cement, glass, and lime factories, can cause perforations. Individuals working with swimming pool chemicals or in chemical factories are also at high risk. Prevention of nasal injury in these working situations would entail wearing proper filter masks during the irritant exposure. Any such irritant can cause more damage if the nose is further dried by the environment or by smoking.
Approach to a patient with nasal septal ulceration History and examination The list of disorders in Table 1 is a good starting point, and it is fairly easy to differentiate the acute (b 6 weeks duration) and chronic (N 6 weeks duration) etiologic factors. In endemic areas TB, leprosy, and leishmaniasis are common causes whereas in immunocompromised cases deep fungal infections should be investigated. Syphilis is a rare cause and is probably of historical interest. A history of any previous nasal surgery or instrumentation, previously treated epistaxis, nose picking, internal and external nasal trauma, use of over-the-counter or prescription nasal sprays, illicit drug abuse like cocaine, and of smoking or other hazardous aerosol exposures should be established. Occupational history to rule out exposure to chemicals such as chrome, agricultural dust, or chemical dust should also be elicited.
Investigations and treatment A battery of investigations may be performed to come to a definite diagnosis of the nasal septal ulceration and
Nasal ulceration perforation and are detailed below, though a disease specific tabulation is also given as a ready reckoner in Table 2. • Laboratory tests: Complete blood count, basic metabolic panel, erythrocyte sedimentation rate, angiotensin-converting enzyme, antineutrophil antibodies, ANA, dsDNA, Anti-Sm, rheumatoid factor, anti-Ro and anti-La antibodies, Epstein-Barr virus antibodies, coccidiomycosis serology, HIV antibodies, VDRL, TPHA, fluorescent treponemal antibody absorption, classic antineutrophil cytoplasmic antibodies, perinuclear antineutrophil cytoplasmic antibody, proteinase 3, and myeloperoxidase; • Biopsy and cultures for fungal, mycobacterial, and bacterial species; • Chest X ray, mantoux test; • Skin testing for anergy; • CT scan of the nose and paranasal sinuses; • Nasal endoscopy; and • Biopsy of the perforation: The biopsy specimen of the septum should be taken from the posterior edge of the perforation, making sure to include enough tissue so that the pathologist has a specimen away from the perforation edge so that a definitive diagnosis can be opined. It is important not to perform the biopsy at the superior edge of the perforation where one would increase the vertical perforation height, which is more difficult to close. Similarly, biopsies at the anterior portion should be avoided, because that area needs to be closed to decrease symptoms.
Value of biopsy in a case of nasal septal ulceration and perforation In the past, nasal biopsy was considered a mandatory part of investigation of nasal septal ulceration and perforation. It has been found that histologic results are most of the time nonspecific and not useful in further management of patients. One study found that in 63 out of 65 patients biopsied, none had a histologic result, which changed the diagnosis of the patient made before biopsy.47 In only two patients with malignancy was the biopsy found to be useful in diagnosis. In another study where 71 patients were biopsied, 12 showed chronic inflammation, six showed acute inflammation, four had acute or chronic inflammation, and trauma was found in 9 cases.6 No evidence of malignancy or vasculitis was found. The biopsy did not help in further management of patients and in vasculitis, tests like cytoplasmic antineutrophil cytoplasmic antibody test and clinical features of vasculitis helped better in diagnosing the disorders. In most cases of rheumatic diseases or vasculitis, biopsy shows only chronic inflammation,48 but as a biopsy has a high predictive value when it is positive in vasculitis, it should be done in all suspect cases.49 The therapy depends on the cause and a brief overview is given below (Table 2). A multidisciplinary approach is
825 needed and the role of an ENT surgeon, and a reconstructive surgeon is required for resolving the issue of the persistent nasal defect that ensues in most cases.
Conclusions Nasal septal ulceration is a diagnostic dilemma due to an extensive differential diagnosis (Table 1) and vague presenting signs and symptoms. The multifarious etiologies can be a challenge to the clinician, and sometimes the exact cause depends on who the consulting specialist is, which could be the ENT surgeon or the dermatologist. Infections are the most satisfying to treat but in nonendemic areas, neoplastic cases may be more common. Vasculitis is probably as common as malignancy. The diagnosis may often require a thorough investigation and multiple tissue specimens from various sites, and in chronic cases, a suspicion of lymphoma should be considered. In spite of the most advanced diagnostic tests, occasionally no cause may be found, which highlights the need for more studies on this vexing clinical problem.50
References 1. Mercurio GA. Anatomic considerations of nasal blood supply. Ear Nose Throat J. 1981;60:443-446. 2. Lanier B, Kai G, Marple B, Wall GM. Pathophysiology and progression of nasal septal Perforation. Ann Allergy Asthma Immunol. 2007;99:473-480. 3. Chrome ulceration of the nasal septum. 1963;1:1364-1365. 4. Oberg D, Akerlund A, Johansson L, Bende M. Prevalence of nasal septal perforation: The Skovde population-based study. Rhinology. 2003;41:72-75. 5. Lin SC, Tai CC, Chan CC, Wang JD. Nasal septum lesions caused by chromium exposure among chromium electroplating workers. Am J Ind Med. 1994;26:221-228. 6. Diamantopoulos II, Jones NS. The investigation of nasal septal perforations and ulcers. J Laryngol Otol. 2001;115:541-544. 7. Kuriloff DB. Nasal septal perforations and nasal obstruction. Otolaryngol Clin North Am. 1989;22:333-350. 8. Stoksted P, Vase P. Perforations of the nasal septum following operative procedures. Rhinology. 1978;16:123-138. 9. Kridel RWH. Considerations in the etiology, treatment, and repair of septal perforations. Facial Plast Surg Clin North Am. 2004;12: 435-450. 10. Dubois EL. Lupus Erythematosus: A Review of the Current Status of Discoid and Systemic Lupus Erythematosus and Their Variants. New York: McGraw-Hill Book Company. 1966. 11. Tuffanelli DL, Dubois EL. Cutaneous manifestations of systemic lupus erythematosus. Arch Derm. 1964;90:377-386. 12. Alcala H, Alarcon-Segovia D. Ulceration and perforation of the nasal septum in systemic lupus erythematosus. N Engl J Med. 1969;281:722-723. 13. Reiter D, Myers AR. Asymptomatic nasal septal perforations in systemic lupus erythematosus. Ann Otol Rhinol Laryngol. 1980;89:78-80. 14. Wegener F. Uber eine eigenartige Rhinogene granulomatose mit besonderer Beteiligung des Arteriensystems und der Nieren. Beitr Pathol Anat. 1939;102:36-68. 15. Tami TA. Granulomatous diseases and chronic rhinosinusitis. Otolaryngol Clin North Am. 2005;38:1267-1278.
826 16. McCaffrey TV. Nasal manifestations of systemic diseases. Otolaryngol Pol. 2009;63:228-235. 17. Yanardag H, Pamuk ON, Pamuk GE. Lupus pernio in sarcoidosis: Clinical features and treatment outcomes of 14 patients. J Clin Rheumatol. 2003;9:72-76. 18. Hammond BL, Kataria YP. Nasal sarcoidosis with septal perforation. J Otolaryngol. 1980;9:31-34. 19. Baum ED, Boudousquie AC, Mrza N. Sarcoidosis with nasal obstruction and septal perforation. Ear Nose Throat J. 1998;77:896-898. 20. McCaffrey TV. Sarcoidosis of the nose. In: McCaffrey TV, ed. Systemic Disease and the Nasal Airway. Thieme; 1993. 21. Kriskovich MD, Kelly SM, Jackson WD. Nasal septal perforation: A rare extraintestinal manifestation of crohn’s disease. Ear Nose Throat J. 2000;79:520-523. 22. Pochon N, Dulguerov P, Widgren S. Nasal manifestations of Crohn’s disease. Otolaryngol Head Neck Surg. 1995;113:813-815. 23. Powell FC, Schroeter AL, Su WP, Perry HO. Pyoderma gangrenosum: A review of 86 patients. Q J Med. 1985;55:173-186. 24. Matsumura T, Matsumura KCS, Ota M, et al. Two cases of pyoderma gangrenosum complicated with nasal septal perforation. Br J Dermatol. 1999;141:1133-1135. 25. Kennedy KS, Prendergast ML, Sooy CD. Pyoderma gangrenosum of the oral cavity, nose, and larynx. Otolaryngol Head Neck. 1987;97:487-490. 26. Hanson RD, Olsen KD, Rogers III RS. Upper aerodigestive tract manifestations of cicatricial pemphigoid. Ann Otol Rhinol Laryngol. 1988;97:493-499. 27. Anderson C, Moore J, Kruijshaar M, Abubakar I. Tuberculosis in the UK: Annual Report on Tuberculosis Surveillance in the UK 2008. London: Health Protection Agency. 2008. 28. Kaur S, Thami GP, Singhal SK. Lupus vulgaris causing nasal perforation: Not a thing of the past. Indian J Dermatol Venereol Leprol. 2003;69:182-183. 29. Garg A, Wadhera R, Gulati SP, Singh J. Lupus vulgaris of external nose with septal perforation–a rarity in antibiotic era. Indian J Tuberc. 2010;57:157-159. 30. Raviglione M, Uplekar M. WHO’s new Stop TB Strategy. Lancet. 2006;367:952-955. 31. Masterson L, Srouji I, Kent R, Bath AP. Nasal tuberculosis - an update of current clinical and laboratory investigation. J Laryngol Otol. 2011;125:210-213. 32. Bennett AMD, Patel N, Kotecha B, Okati AA. Septal perforation secondary to Mycobacterium kansasii infection. J Laryngol Otol. 2003;117:992-994. 33. Goguen LA, Karmody CS. Nasal tuberculosis. Otolaryngol Head Neck Surg. 1995;113:131-135.
K. Sadarna, K. Goel 34. Sehgal VN, Sardana K, Sharma S. Inadequacy of clinical and/or laboratory criteria for the diagnosis of lupus vulgaris, re-infection cutaneous tuberculosis: Fallout/implication of 6 weeks of anti-tubular therapy (ATT) as a precise diagnostic supplement to complete the scheduled regimen. J Dermatolog Treat. 2008;19:164-167. 35. Job CK, Chehl S, McCormick GT, et al. Mycobacterium leprae can penetrate nasal mucosa. Indian J Lepr. 1987;59:356-357. 36. Barton RP. Clinical manifestation of leprous rhinitis. Ann Otol Rhinol Laryngol. 1976;85:74-82. 37. Bhat R, Sharma VK, Deka RC. Otorhinolaryngologic manifestations of leprosy. Int J Dermatol. 2007;46:600-606. 38. Husain S, Malaviya GN, Girdhar A, et al. Nasal myiasis in leprosy. Lepr Rev. 1991;62:389-394. 39. McDonald TJ. Nasal manifestations of systemic diseases. In: Cummings CW, ed. Otolaryngology Head and Neck Surgery. 4th ed. Philadelphia: Mosby; 2005. 40. Maisel RH. Sinusitis in the immunocompromised patient. In: McCaffrey TV, ed. Systemic Disease and the Nasal Airway. Thieme; 1993. 41. Toran KC, Sah SP, Joshi A, Rani S. Ulcerative post-kala azar mucosal leishmaniasis masquerading as a carcinoma–a case report. Indian J Pathol Microbiol. 2003;46:487-489. 42. Amini J. Perforation of the nasal septum caused by leishmaniasis. Ann Otolaryngol Chir Cervicofac. 1976;93:691-694. 43. Davison SP, Habermann TM, Strickler JG, et al. Nasal and nasopharyngeal angiocentric T-cell lymphomas. Laryngoscope. 1996;106:139-143. 44. Mendenhall WM, Olivier KR, Lynch Jr JW, Mendenhall NP. Lethal midline granuloma-nasal natural killer/T-cell lymphoma. Am J Clin Oncol. 2006;29:202-206. 45. Williams N. Nasal septal ulceration and perforation in jiggers. Occup Med. 1998;48:135-137. 46. Schoelzel EP, Menzel ML. Nasal sprays and perforation of the nasal septum. JAMA. 1985;253:2046. 47. Murray A, McGarry GW. The clinical value of septal perforation biopsy. Clin Otolaryngol. 2000;25:107-109. 48. Willkens RF, Roth GJ, Novak A, et al. Perforation of nasal septum in rheumatic disease. Arthritis Rheum. 1976;19:119-121. 49. Jennings CR, Jones NS, Dugar J, et al. Wegener’s granulomatosis: A review of diagnosis and treatment in 53 subjects. Rhinology. 1998;36: 188-191. 50. Parker NP, Pearlman AN, Conley DB, et al. The dilemma of midline destructive lesions: A case series and diagnostic review. Am J Otolaryngol. 2010;31:104-109.