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Keywords: larynx, systemic lupus erythematous, systemic sclerosis, mixed connective tissue disease, bamboo node. Abstract: Rheumatic diseases usually promote several systemic disorders, which can affect blood vessels, mucosa and serosa of the aerodigestive tract. IntroductionRheumatic diseases comprise a heterogeneous group of entities producing connective tissue systemic disorders.
The development of diphtheria antitoxin and diphtheria toxoid vaccine led to the near-elimination of diphtheria in Western countries. Cutaneous diphtheria is usually a secondary infection that follows a primary skin lesion due to trauma, allergy, or autoimmunity.
In 1926, Ramon at the Institut Pasteur found that formalinization of diphtheria toxin resulted in the production of diphtheria toxoid, which was nontoxic but highly immunogenic. Characteristic pathologic findings of diphtheria include mucosal ulcers with a pseudomembranous coating composed of an inner band of fibrin and a luminal band of neutrophils.
Although diphtheria is rare in the United States and other developed countries, this diagnosis should be considered in patients who have severe pharyngitis, particularly with difficulty swallowing, respiratory compromise, or signs of systemic disease including myocarditis or generalized weakness.
The systemic manifestations of diphtheria stem from the effects of diphtheria toxin and include weakness as a result of neurotoxicity and cardiac arrhythmias or congestive heart failure due to myocarditis.
This is a variable dermatosis most often characterized by punched-out ulcerative lesions with necrotic sloughing or pseudomembrane formation (Fig.
Airway obstruction poses a significant early risk in patients presenting with advanced diphtheria.
Neurologic manifestations may appear during the first or second week of illness, typically beginning with dysphagia and nasal dysarthria and progressing to other signs of cranial nerve involvement, including weakness of the tongue and facial numbness.
Other complications of diphtheria include pneumonia, renal failure, encephalitis, cerebral infarction, and pulmonary embolism. The diagnosis of diphtheria is based on clinical signs and symptoms plus laboratory confirmation. A diagnosis of cutaneous diphtheria requires laboratory confirmation since the lesions are not characteristic and are clinically indistinguishable from other dermatoses. Prompt administration of diphtheria antitoxin is critical in the management of respiratory diphtheria.
Antibiotics are used in the management of diphtheria primarily to prevent transmission to other susceptible contacts.
A clinical study in Vietnam found that penicillin was associated with a more rapid resolution of fever and a lower rate of bacterial resistance than erythromycin; however, relapses were more common with penicillin. Patients who recover from respiratory or cutaneous diphtheria should have antitoxin levels measured. Patients in whom diphtheria is suspected should be hospitalized in respiratory isolation rooms, with close monitoring of cardiac and respiratory function. Fatal pseudomembranous diphtheria typically occurs in patients with nonprotective antibody titers and in unimmunized patients.
Sustained campaigns for vaccination of children and adequate boosting vaccination of adults are responsible for the exceedingly low incidence of diphtheria in most developed nations. Close contacts of diphtheria cases should undergo throat culture to determine whether they are carriers. Contacts of diphtheria cases who have an uncertain immunization status should receive the appropriate diphtheria toxoid–containing vaccine. Nondiphtherial corynebacteria, which are also referred to as diphtheroids or coryneforms, are a widely diverse collection of bacteria that are taxonomically lumped together on the basis of their 16S rDNA signature nucleotides.
These organisms are non-acid-fast, catalase-positive, aerobic or facultatively anaerobic bacilli. This organism causes a diphtheria like illness and produces both diphtheria toxin and a dermonecrotic toxin.
After a 1976 survey of diseases caused by nondiphtherial corynebacteria, CDC Group JK was recognized as an important opportunistic pathogen among neutropenic patients and later emerged in HIV-infected patients as an AIDS-associated opportunistic infection. Erythrasma is a cutaneous infection producing reddish-brown, macular, scaly, pruritic intertriginous patches. Centers for Disease Control and Prevention: Availability of diphtheria antitoxin through an investigational new drug protocol. Kadirova R et al: Clinical characteristics and management of 676 hospitalized diphtheria cases, Kyrgyz Republic, 1995. MacGregor RR: Corynebacterium diphtheriae, in Principles and Practice of Infectious Diseases, 6th ed, GL Mandell et al (eds).
McNeil SA et al: Comparison of the safety and immunogenicity of concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults. Meyer DK, Reboli AC: Other coryneform bacteria and Rhodococcus, in Principles and Practice of Infectious Diseases, 6th ed, GL Mandell et al (eds).
Pichichero ME et al: Combined tetanus, diphtheria, and 5-component pertussis vaccine for use in adolescents and adults. Galazka A: Implications of the diphtheria epidemic in the former Soviet Union for immunization programs.
Tracheostomy Care Adapted from various resources (see reference slide) by Ambercare Education Department April 14, 2014. Hives (medically known as urticaria) are itchy, erythematous (reddish), often elevated skin lesions that blanch with pressure. They are red, itchy, raised areas of skin that appear in varying shapes and sizes. The skin lesions of urticarial disease are caused by an inflammatory reaction in the skin, causing leakage of capillaries in the dermis, and resulting in an edema which persists until the interstitial fluid is absorbed into the surrounding cells.Urticaria are caused by the release of histamine and other mediators of inflammation (cytokines) from cells in the skin.
Angioedema often results from a similar release of mediators, involving the skin’s deeper cutaneous and sub-cutaneous tissues. Scarce laryngeal involvement has been described in these patients and this study aims at investigating laryngeal alterations found in patients with rheumatic diseases. Most often, isolates from cases of cutaneous disease lack the tox gene and therefore do not express diphtheria toxin. Subsequent studies showed that immunization with diphtheria toxoid elicited antibodies that neutralized the toxin and prevented most manifestations of diphtheria. In populations where a majority of individuals have protective antitoxin titers, the carrier rate for toxigenic strains of C.
Initially white and firmly adherent, in advanced diphtheria the pseudomembranes turn gray and even green or black as necrosis progresses.
Pseudomembranes may slough and obstruct the airway or may advance to the larynx or into the tracheobronchial tree.
During the outbreak in the Kyrgyz Republic in 1995, myocarditis was seen in 22% and neuropathy in 5% of hospitalized patients.
Ciliary paralysis, which is typical, manifests as blurred vision due to paralysis of pupillary accommodation, with a preserved light reflex.
Respiratory diphtheria should be considered in patients with sore throat, pharyngeal exudates, and fever. The antitoxin—a horse antiserum—is effective in reducing the extent of local disease as well as the risk of complications of myocarditis and neuropathy. Erythromycin therapy targets protein synthesis and thus offers the presumed benefit of stopping toxin synthesis more quickly than a cell wall–active ?-lactam agent. If diphtheria antitoxin has been administered, this test should be performed 6 months later. At present, diphtheria toxoid vaccine is coadministered with tetanus (with or without acellular pertussis) vaccine. After samples for throat culture are obtained, antimicrobial prophylaxis should be considered for all close contacts, even those who are culture-negative.
Tdap (rather than Td) is now recommended as the booster vaccine of choice for adults who have not recently received an acellular pertussis–containing vaccine. The diversity of this group is exemplified by the wide range in guanine-plus-cytosine content (45–70%).
Their colonial morphologies vary widely; some species are small and ?-hemolytic (similar to lactobacilli), whereas others form large white colonies (similar to yeasts). These gram-positive coccobacilli have been associated with tuberculosis-like infections in humans with granulomatous pathology.
Eric Henry, Shaun Kilty, Miklos Matyas, Laurie McLean, Safeena Kherani, Andre Lamothe Otolaryngology—Head. A surgical procedure performed to open an artificial airway in the neck through an incision in the trachea A. FRCS(C) Chief Department of Otolaryngology HNS St Michael’s Hospital University of Toronto POS November.

In this case, more edema (fluid accumulation and swelling) is present than that seen with hives. In homoeopathy, the treatment plan is so designed that it helps in correcting the immune system, in turn treating Urticaria from within. There are excellent medicines in Homoeopathy which help relieve the problem in the most simplisitic manner. In 1976, Smith et al.2 reported ulcerations, stenosis and edema of cricoarytenoid units of two SLE patients. Patients can develop recurrent attacks of swollen tissues, pain in the abdomen, and swelling of the voice box (larynx) which can compromise breathing.
Nevertheless, pockets of colonization have persisted in North America, particularly in South Dakota, Ontario, and Washington state.
In the 1930s, mass immunization of children and susceptible adults commenced in the United States and Europe. Mucosal ulcers result from toxin-induced necrosis of the epithelium accompanied by edema, hyperemia, and vascular congestion of the submucosal base.
The characteristic white pseudomembrane is caused by diphtheria toxin–mediated necrosis of the respiratory epithelial layer, producing fibrinous coagulative exudate. Less commonly, the lesions are detected in the larynx, nares, and trachea or bronchial passages. The mortality rate was 7% among patients with myocarditis as opposed to 2% among those without myocardial manifestations. Cranial neuropathy may be followed by respiratory and abdominal muscle weakness requiring artificial ventilation. Rapid institution of antitoxin therapy is also associated with a significant reduction in mortality risk. Alternative agents for patients who are allergic to penicillin or cannot take erythromycin include rifampin and clindamycin. It is important to treat the underlying cause of the dermatoses in addition to the superinfection with C. In patients with extensive pseudomembranes, consultation with an anesthesiologist or an ear, nose, and throat specialist is recommended because of the possibility that tracheostomy or intubation will be required. DTaP (full-level diphtheria and tetanus toxoids and acellular pertussis vaccine, adsorbed) is the currently recommended vaccine for children up to the age of 7; DTaP replaced DTP (diphtheria and tetanus toxoids and whole-cell pertussis vaccine) in 1997. Although frequently considered colonizers or contaminants, the nondiphtherial corynebacteria have been associated with invasive disease, particularly in immunocompromised patients.
This organism appears to be the etiologic agent of a severe urinary tract syndrome known as alkaline-encrusted cystitis: a chronic inflammatory bladder infection associated with deposition of ammonium magnesium phosphate on the surface and walls of ulcerating lesions in the bladder.
This nontoxigenic organism is occasionally identified as a source of invasive infection in immunocompromised or postoperative patients and prosthetic joint recipients.
A few human cases of sepsis, endocarditis, septic arthritis, pneumonia, meningitis, and empyema have been reported. Homoeopathic remedies not only help relieve the acute condition but also reduce the incidents of urticarial episodes and cure completely. Material and method: A transversal study was developed with systemic lupus erythematous, systemic sclerosis and mixed connective tissue disease's patients. C1 inhibitor deficiency, complement esterase deficiency, giant urticaria, hereditary angioedema, Quincke's edema. The toxin is associated with the formation of pseudomembranes in the pharynx during respiratory diphtheria. The incubation period for respiratory diphtheria is 2–5 days; however, disease can develop as long as 10 days after exposure. In contrast to respiratory disease, cutaneous diphtheria is not a reportable disease in United States. The toxin is produced in the pseudomembranous lesion and is taken up into the bloodstream, through which it is distributed to all organ systems. Nevertheless, individuals with nonprotective titers may contract diphtheria through either travel or exposure to individuals who have recently returned from regions where the disease is endemic.
The presence of a pharyngeal pseudomembrane or an extensive exudate should prompt consideration of diphtheria (Fig.
The Centers for Disease Control and Prevention (CDC) recognizes confirmed respiratory diphtheria (laboratory proven or epidemiologically linked to a culture-confirmed case) and probable respiratory diphtheria (clinically compatible but not laboratory proven or epidemiologically linked). Several weeks later—sometimes as cranial neuropathy is improving—a generalized sensorimotor polyneuropathy may appear, with prominent autonomic manifestations (including hypotension) in some cases.
Patients in whom cutaneous diphtheria is identified should have the nasopharynx cultured for C. Because diphtheria antitoxin cannot neutralize cell-bound toxin, prompt initiation is important. Another important predictor of fatal outcome is the interval between local disease development and antitoxin administration. Tdap is a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine formulated for adolescents and adults. Specifically, for example, these organisms have been implicated in bacteremia, particularly in association with catheterization, endocarditis, prosthetic valve infection, meningitis, neurosurgical shunt infection, brain abscess, peritonitis (often in the setting of chronic ambulatory peritoneal dialysis), osteomyelitis, septic arthritis, urinary tract infection, empyema, and pneumonia.
The organism causes exudative pharyngitis, primarily during summer months, in rural areas, and among individuals exposed to cattle. The gram-positive coccobacilli, which slightly resemble streptococci, grow as small, gray to white, glistening, nonhemolytic colonies on blood agar.
The agent is susceptible to ?-lactams, tetracycline, aminoglycosides, and fluoroquinolones. This organism appears to be a commensal of the human nasopharynx and skin but has been implicated as a cause of pharyngitis and chronic skin ulcers. Angioedema of the GI tract can cause severe abdominal pain, while angioedema of the larynx or tongue can lead to respiratory distress. In a study with 45 patients with fairly severe rheumatoid arthritis (RA) submitted to indirect laryngoscopy, Lawry et al.4 detected abnormalities in 52% of cases. While toxigenic strains most frequently cause pharyngeal diphtheria, nontoxigenic strains commonly cause cutaneous disease. Once bound to its cell surface receptor (a heparin-binding, epidermal growth factor–like precursor), the toxin is internalized by receptor-mediated endocytosis and enters the cytosol from an acidified early endosomal compartment. Ulcers and pseudomembranes in severe respiratory diphtheria may extend from the pharynx into medium-sized bronchial airways.
The pharyngitis is acute in onset, and respiratory obstruction from the pseudomembrane may occur in severe cases.
Patients usually seek medical attention because of nonhealing or enlarging skin ulcers, which may be associated with a preexisting wound or dermatoses such as eczema, psoriasis, and venous stasis disease. Myocarditis is typically associated with dysrhythmia of the conduction tract and dilated cardiomyopathy. The clinical syndrome and the findings on lumbar puncture of raised levels of protein without pleocytosis in cerebrospinal fluid resemble Guillain-Barre syndrome (Chap. Once a clinical diagnosis of diphtheria is made, diphtheria antitoxin should be administered as soon as possible. Treatment with glucocorticoids has not been shown to reduce the risk of myocarditis or polyneuropathy. Cutaneous diphtheria has a low mortality rate and is rarely associated with myocarditis or peripheral neuropathy. Tdap was licensed for use in the United States in 2005 and is the recommended booster vaccine for children 11–12 years old and the recommended catch-up vaccine for children 7–10 and 13–18 years old.
Patients infected with nondiphtherial corynebacteria usually have significant medical comorbidity or immunosuppression.
The organism is an important veterinary pathogen, causing suppurative lymphadenitis, abscesses, and pneumonia, but is rarely a human pathogen.
In addition, this fluorescent microbe has been associated with bacteremia in patients with hematologic malignancy. Results: Twenty-seven patients were included in the study, 26 succeeded in completing the videolaryngoestroboscopy.
Diseases such as scleroderma and Sjogren's syndrome have also presented laryngeal involvement. Treatment options include antihistamines and male steroids (androgens) that can also prevent the recurrent attacks. In the United States and Europe, diphtheria has been controlled in recent years with effective vaccination, although sporadic outbreaks have occurred. In addition to older age and lack of vaccination, risk factors for diphtheria outbreaks include alcoholism, low socioeconomic status, crowded living conditions, and Native American ethnic background.

In vitro, the toxin may be separated into two chains after digestion with serine proteases: the N-terminal A fragment and the C-terminal B fragment. Inoculation of pseudomembrane fragments or submembranous swabs onto Loffler's or tellurite selective medium reveals C. Throat samples should be submitted to the laboratory for culture with the notation that diphtheria is being considered. The laboratory media for cutaneous diphtheria are the same as those used for respiratory diphtheria: Loffler's or Tinsdale's selective medium in addition to nonselective medium such as blood agar.
Successful treatment with erythromycin or tetracycline has been reported, with surgery also performed when indicated. Erythrasma responds to topical erythromycin, clarithromycin, clindamycin, or fusidic acid, although more severe infections may require oral macrolide therapy. Also nontoxigenic, this organism has been associated with invasive opportunistic infections in severely ill or immunocompromised patients.
Laryngeal abnormalities were seen in 11 of 12 patients with lupus, in all 11 patients with sclerodermia and in 3 patients with mixed connective tissue disease. Diphtheria is still common in the Caribbean, Latin America, and the Indian subcontinent, where mass immunization programs are not enforced. An outbreak that occurred in Seattle in 1972–1982 included 1100 cases, primarily manifesting as cutaneous disease. Delivery of the A fragment into the eukaryotic cell cytosol results in irreversible inhibition of protein synthesis by NAD+-dependent ADP ribosylation of elongation factor 2.
Unlike the exudative lesion associated with streptococcal pharyngitis, the pseudomembrane in diphtheria is tightly adherent to the underlying tissues.
Pathologically, diphtheria neuropathy is a noninflammatory demyelinating disorder mediated by the exotoxin. This information should prompt cultivation on special selective medium and subsequent biochemical testing to differentiate C. As has been mentioned, respiratory diphtheria remains a notifiable disease in the United States, whereas cutaneous diphtheria is not. For patients in whom the organism is not eradicated after a 14-day course of erythromycin or penicillin, an additional 10-day course followed by repeat culture is recommended. Adults who have received acellular pertussis vaccines should continue to receive decennial Td booster vaccinations.
Nevertheless, treatment with antitoxin and antibiotics should be initiated when respiratory C. Vocal fold bamboo node was observed in 5 patients and 92.3% of all patients presented laryngeal signs of gastroesophageal reflux disease. Large epidemics have occurred in the independent states formerly encompassed by the Soviet Union.
In temperate regions, respiratory diphtheria occurs year-round but is most common during winter months. Occasionally, weakness, dysphagia, headache, and voice change are the initial manifestations. Effective therapy involves removal of the source of infection, be it a catheter, a prosthetic joint, or a prosthetic valve. Conclusion: We noticed 5 vocal fold bamboo nodes and gastroesophageal reflux disease in almost all patients.
Relative to race, 13 were Mulatto, 7 were Black and 6 were Caucasian.Patients were included in the study as volunteers, regardless of presence of laryngeal disorder and duration of disease. Corynebacteriophage beta carries the structural gene (tox) encoding diphtheria toxin, and a family of closely related corynebacteriophages are responsible for toxigenic conversion of tox– C. Neck edema and difficulty breathing are seen in more advanced cases and carry a poor prognosis. Hoarseness suggests laryngeal diphtheria, in which laryngoscopy may be diagnostically helpful. The current protocol for the use of antitoxin includes a test dose to rule out immediate-type hypersensitivity. The related organism Rhodococcus equi is associated with necrotizing pneumonia and granulomatous infection, particularly in immunocompromised individuals. Patients who exhibit hypersensitivity require desensitization before a full therapeutic dose of antitoxin is administered.
Other related species that can cause infections in humans are Actinomyces (formerly Corynebacterium) pyogenes and Arcanobacterium (formerly Corynebacterium) haemolyticum. Moreover, lysogenic conversion from a nontoxigenic to a toxigenic phenotype has been shown to occur in situ.
Given that the ET8 complex expressed a toxin against which the prevalent diphtheria toxoid vaccine was effective, the epidemic was attributed to failure of the public health infrastructure to effectively vaccinate the population. These infections may be successfully treated with a wide variety of antibacterial agents, including ?-lactams, rifampin, aminoglycosides, or vancomycin; however, the organism appears to be resistant to fluoroquinolones, macrolides, and tetracyclines. The organism is susceptible to ?-lactams, macrolides, fluoroquinolones, clindamycin, vancomycin, and doxycycline. During the epidemic, the incidence rate was high among individuals from >15 years of age up to 50 years of age. Socioeconomic instability, migration, deteriorating public health programs, frequent vaccine shortages, delays in implementation of vaccination and of treatment in response to cases, and lack of public education and awareness were contributing factors in that outbreak.
The most frequent alteration found in 11 patients was the presence of edema and thickening of the interarytenoid region, which has been described as a sign of gastroesophageal reflux disease (GERD) (Figure 1). Among these patients, 9 presented clinical complaints of globus pharyngeus, hoarseness and dry cough.Other 3 patients showed yellowish and transversal deposit lesions of lamina propria, classically referred as "bamboo nodules" (Figures 2 and 3).
A small unilateral vocal sulcus was observed in another patient.All patients (11) with scleroderma presented laryngeal alterations (Table 2).
Alterations suggestive of GERD were observed in 11 patients, out of which 6 had clinical complaints. Human infections—particularly endocarditis of either prosthetic or native valves and invasive pneumonia—have been identified only rarely. The organism has been identified most commonly in pulmonary infections, but infections of brain, bone, and skin have also been reported. Signs of laryngeal hypertrophy were observed in 1 patient (vocal fold hypertrophy on the prominence of vocal processes).Out of 3 patients with MCTD, 2 presented "bamboo nodules" and 2 showed alterations suggestive of GERD (Table 3).
Ten out of 26 patients presented hoarseness and 5 complained of dysphagia.DiscussionLaryngeal alterations in patients with rheumatic diseases have been described and may be present in different diseases and in varied forms. The authors support the fact that these alterations may be a sign of imminent exacerbation of disease similarly to other indicators of inflammatory activity.In our study, out of 12 patients with SLE, 3 exhibited rheumatoid vocal nodules, which are disorders found in the list of 9 categories previously described. Although scarce cases of rheumatoid nodules have been described some decades ago, Hosako-Naito et al.6 were the most dedicated group to study these lesions. The authors reported two cases of suspected autoimmune disease with laryngological findings of "bamboo nodules" and support nomenclature standardization for bamboo vocal nodules. Histologically, this lesion shows areas of linear granulomas with central necrosis surrounded by macrophages5. However, the laryngoscopic view of lesion is very similar to an intracordal cyst, even when examined by an expert professional.We identified 1 patient with bowed vocal folds and arytenoid cartilages presenting prominent vocal processes. Regardless of the typical aspects of presbylarynx in these findings, we believe that they are caused by rheumatic disease, considering that the patient was 54 years of age. The organism is routinely susceptible to vancomycin, which is considered the drug of choice. Wolman et al.7 performed a post-mortem study in 8 patients with rheumatoid arthritis and verified that they all had histological signs of neurogenic muscle atrophy. In addition, 4 patients showed signs of chronic myositis associated with nerve degeneration.So far, our study seems to be unique in assessment of patients with SLE, scleroderma and MCTD, regardless of presence of laryngeal complaint and of dysphonic process.
Out of 26 patients, alterations were verified in 8 cases, which, we believe, are laryngeal manifestations of rheumatic diseases: 5 lesions suggestive of bamboo vocal nodules, 2 vocal folds with blood vessels dilatation, and 1 patient with hypertrophy of the thyroarytenoid muscle.
Perhaps esophageal involvement by rheumatic disease, associated with frequent use of medicines that predispose to GERD, is responsible for the increased number of patients with GERD signs.Figure 1.
Bamboo nodule on the middle third of the right vocal fold (Arrow).ConclusionIn this study, we could observe laryngeal lesions related to rheumatic diseases in 8 of 26 patients assessed. We also identified 5 lesions suggestive of "bamboo nodules", which represent the greatest number ever described.

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