|Year : 2016 | Volume
| Issue : 2 | Page : 83-90
Soft tissue infection of the head and neck in HIV –A vexing diagnostic conundrum
R Keerthi, Tulasi Nayak
Department of Oral and Maxillofacial Surgery, Vokkaligara Sangha Dental College and Hospital, Bengaluru, Karnataka, India
|Date of Web Publication||19-May-2016|
Department of Oral and Maxillofacial Surgery, Vokkaligara Sangha Dental College and Hospital, K.R. Road, V. V. Puram, Bengaluru - 560 004, Karnataka
Necrotizing soft tissue infections (NSTI) are a spectrum of aggressive and devastating conditions with a high mortality rate. Immunocompromised patients are highly susceptible to these infections and may manifest unusual variants and varied combinations of the various conditions in this spectrum. We present here an unusual case of NSTI of the head and neck in an HIV-positive patient, highlighting the difficulty in diagnosis and the importance of lab risk indicator for necrotizing fasciitis scoring and swift, aggressive surgical therapy.
Keywords: HIV, lab risk indicator for necrotizing fasciitis, Ludwig's angina, necrotizing fasciitis, necrotizing soft tissue infection
|How to cite this article:|
Keerthi R, Nayak T. Soft tissue infection of the head and neck in HIV –A vexing diagnostic conundrum. SRM J Res Dent Sci 2016;7:83-90
|How to cite this URL:|
Keerthi R, Nayak T. Soft tissue infection of the head and neck in HIV –A vexing diagnostic conundrum. SRM J Res Dent Sci [serial online] 2016 [cited 2020 Oct 22];7:83-90. Available from: https://www.srmjrds.in/text.asp?2016/7/2/83/182670
| Introduction|| |
Necrotizing soft tissue infection (NSTI) describes a variety of extremely aggressive and potentially life-threatening bacterial soft tissue infections., NSTIs are often deep and devastating and involve the fascial and/or muscle compartments. The release of toxins and massive cytokine efflux due to widespread tissue destruction contribute to the multi-organ failure and high mortality.
Ustin and Malangoni have classified the large spectrum of diseases under NSTIs into three types based on the microbiology., Among which are necrotizing fasciitis (NF) (Type II) and Ludwig's angina (Type I).
NSTIs occur predominantly in patients predisposed by immune compromise, diabetes mellitus, or vascular insufficiency. Mortality can be reduced by early diagnosis and aggressive surgical therapy.
We describe here a case of a previously undiagnosed HIV patient who presented with NF of the right upper chest wall and Ludwig's angina concurrently.
| Case Report|| |
A 30-year-old male patient, presented with a chief complaint of swelling in the neck along with pus exudation over the right half of the chest. He gave a history of the appearance of multiple fluid-filled vesicles over the left chest and shoulder 3 weeks prior, for which he had approached a local holistic healer. The healer had given him some powder to apply over the lesions following which the patient had experienced some relief. About 1 week before the hospital visit, similar lesions reappeared, this time over the right upper chest together with a large disfiguring swelling which appeared on the neck. This time, the healer advised him to approach a physician who in turn treated him with intravenous (IV) penicillin injections. The symptoms did not regress and instead, a small coin sized, black, foul smelling, crusted lesion began developing over the upper right chest region which gradually spread toward the shoulder and down onto the chest. This occurred concomitantly with the consolidation of the neck swelling. The patient was then referred to our hospital. There was no history of systemic illnesses or long-term medication use. The patient gave no history of a toothache or difficulty in breathing. On examination, the patient was febrile, hypotensive, tachycardic, and delirious. A large, erythematous, brawny swelling was noted bilaterally at the submandibular and submental region. An eschar was noted at the right shoulder and chest (20 cm in length) extending to the midline [Figure 1] and [Figure 2]. The area around the eschar, extending up to the abdomen showed crepitus and was insentient. Multiple scars were present on the left chest. A small abrasion measuring 1 cm × 1 cm was noted at the right postauricular region. An intraoral examination showed an absence of caries, periodontal disease, ulcers and other signs of infection. A thorough ENT examination showed no focus of infection. Based on the clinical manifestation of the lesions and the history, the patient was provisionally diagnosed with disseminated herpes zoster superinfected with bacteria along with Ludwig's angina of ambiguous origin. Resuscitation with IV fluids, colloids, and inotropic agents was done promptly, and the patient was empirically started on a combination of amoxicillin with clavulanate and clindamycin as well as acyclovir for possible dental and herpes zoster infections. Disseminated zoster suggested the possibility of an immunocompromised status and a battery of test were ordered [Table 1].
|Figure 1: Large swelling in the neck and necrosis on the right shoulder area|
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|Figure 2: Following incision and drainage at the right submandibular region|
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The blood investigations showed that the patient was HIV positive (ELISA kit) and was started on anti retroviral therapy (zidovudine 300 mg, lamivudine 150 mg and efavirenz 600 mg) for HIV. However, the negative Tzanck test, a lack of response to the empirical antiviral and antibiotic regimen, negative Mantoux test, negative sputum test for acid-fast bacilli, negative gram's test, and negative potassium hydroxide mount excluded the previous as well as alternative diagnosis of cutaneous tuberculosis, cutaneous anthrax as well as fungal infections. Lab risk indicator for necrotizing fasciitis (LRINEC) score of more than eight suggested a high possibility of NF. This prompted us to immediately explore the area surgically. The surgical debridement of the eschar over the right chest showed the involvement of subcutaneous tissue until the abdomen. Necrotic tissue was debrided until fresh bleeding was seen. The tissues showed a characteristic lack of resistance and about 50 ml of dishwater pus was drained. The edge of the lesion was biopsied, which revealed nonspecific inflammatory cells interspersed with necrotic tissue. Microbiologic study revealed no microbial growth. The large ulcer on the chest was treated with peroxide wash and gauze dressings for 3 weeks until fresh granulation tissue was seen at the base of the lesion [Figure 3].
The Ludwig's angina appearing with NF was more troublesome. The presence of the neck swelling, as well as the impending development of NF on the chest, increased the morbidity of the patient. The culture and sensitivity of the pus aspirated from the submandibular space showed sensitivity to cotrimoxazole and levofloxacin. Hence, the antibiotics were switched to cotrimoxazole. An incision and drainage of the collection within the submandibular and submental regions was done using standard precautions [Figure 2]. About 30 ml of frank pus was drained, and the wound was regularly dressed with iodoform gauze packs. The swelling in the neck subsided within a week.
The diagnosis in our case was considerably difficult due to the multiple clinical findings, the immunocompromised state of the host and the lack of a clear etiology [Timeline]. Were the swellings on the neck and the necrosis on the chest occurring due to a single cause? Or was one responsible for the other? Had the two conditions occurred separately or was this a presentation of ascending NF? The lack of financial resources prevented us from obtaining a computed tomography (CT) of the head and neck region instead meticulous clinical examination, simple, inexpensive tests and ultrasound were obtained. Time was of the essence as the lab investigations, and the impending airway compromise pointed toward a grave prognosis. Postoperatively, we concluded that the NF of the chest and the Ludwig's angina were two separate entities which occurred simultaneously and the scars on the opposite side of the chest could have been a separate presentation of varicella zoster infection. The baffling presentation of three infections occurring concomitantly could have been due to the immunocompromised status of the patient.[INLINE 1]
| Discussion|| |
The initial presentation of the various forms of NSTIs is similar. As the disease progresses, the presentation becomes characterized. Wang et al. described an early stage with manifestations of edema, erythema, tenderness, pain beyond the confines of erythema and a late stage with manifestations of crepitus, skin anesthesia, and skin necrosis/discoloration.
The other “hard signs” of NSTI are bullae, skin ecchymosis or sloughing, gas in the tissues, crescendo pain, rapidly spreading infection, and symptoms of sepsis such as hypotension, tachycardia, and organ., These, however, may not be typical in immunocompromised patients.
Etiology and pathogenesis
NF is a relatively rare infection, characterized by rapidly progressing necrosis of the fascia and subcutaneous fat, with subsequent necrosis of the overlying skin. It is the fastest spreading disease known to man with a progression rate of up to 3 cm/h. The incidence of this disease increases with age (median age 57 years), and most adult cases (70%) occur in patients with at least one underlying chronic illness. Immunocompetence has been claimed to be an important factor in the etiopathogenesis of NF.,,
The most commonly associated etiological factors include IV drug abuse, postoperative complications, traumatic wounds, and minor trauma. Nonsteroidal anti-inflammatory drugs  and hematogenous infection distant foci , are also other purported causes. Taviloglu et al., in their retrospective study reported a 61% incidence of idiopathic NF, which they noted could have been due to unrecognized minor trauma in patients with chronic, debilitating diseases. It is generally agreed that NF occurs due to microbial invasion through external trauma or direct spread from a perforated viscus.,
Ludwig's angina is a rapidly progressing necrotizing cellulitis affecting the posterior oropharynx, submaxillary, and sublingual spaces. Usually, it presents as a hot, red, edematous, sharply defined eruption which may progress to NF and gangrene. Cellulitis is distinguished in three forms; moderately severe form, in severe form (presence of systemic manifestations) and high danger form (localized in the extremities or head of immunosuppressed patients). The toxic products trigger dendritic cells of Langerhans to secrete interleukin (IL)-1 and tumor necrosis factor (TNF)-α which, in turn, increase bacterial phagocytosis. Most affected patients are between age 20 and 60 years with a male predominance (3:1–4:1). Typically arising from an odontogenic source, the affected structures in order of most frequent contamination are the anterior neck, the pharyngomaxillary space, the retropharynx, and the superior mediastinum. The fascial layers may limit the spread of infection. However, the spaces of the neck communicate with one another forming avenues by which infections may spread over large areas.
NF generally presents with gross edema, gas, ulceration, a bronze discoloration and foul odor. There is a characteristic production of “dishwater pus” which is a toxin-mediated suppression of polymorphonuclear leukocytes. Gas denotes the presence of anaerobic bacteria and presents as crepitus. Although crepitus is commonly found, the absence must not be taken as a reassuring sign. Clinically, NF exhibits three zones, a central black necrotic area surrounded by a zone of tender purple skin followed by a wide peripheral zone of erythema. The area of necrosis often extends beyond what is anticipated, as thrombosis of the dermal capillary beds precedes skin necrosis. Altered oxygen tension and muscle hypoxia with increasing intracompartmental pressures can sometimes lead to compartment syndrome.
The LRINEC score described by Wong et al., in 2004 describes the probability of NF by measuring the biochemical changes in the patient's blood and predicts severity of sepsis. The total scores are calculated to assess the risk of NF in the patient. Low risk: Score 5, moderate risk: Score 6–7, and high risk: Score <8. Patients with an LRINEC score of ≥6 have an increased probability of NF. This scoring system was essential to us to conclude that the patient was exhibiting signs of NF [Table 2].
Ludwig's angina presents as a large brawny swelling involving the neck spaces bilaterally. The most dangerous complication of Ludwig's angina is airway obstruction which occurs rapidly due to elevation and swelling of the tongue. Other known complications include cavernous sinus thrombosis, brain abscess, carotid sheath infection and rupture, suppurative thrombophlebitis of the internal jugular vein, mediastinitis, empyema, pericardial and/or pleural effusion, osteomyelitis of the mandible, subphrenic abscess, and aspiration pneumonia.,
Fine-needle aspiration cytology with an associated Gram-stain can identify bacteria in the soft tissues. Occasionally, exploratory incision and even frozen-section biopsy have been used to help establish or exclude the diagnosis.
Microbiology and antibiotics
NSTIs are commonly polymicrobial infections with a synergistic interaction between aerobes and anaerobes which work together to evade host defenses and cause tissue damage. The organisms most often isolated in patients with Ludwig's angina are Streptococcus viridans and Staphylococcus aureus. The microbiology of NF is rich with a classification by Morgan, who classified it into four types [Table 3]. The rapidity of the spread may be attributed to immunosuppression in the host.,
Historically, an empiric regimen using high dose penicillin and clindamycin was recommended to cover Gram-positive and anaerobic organisms. A third agent was used for additional empiric coverage of Gram-negative organisms. Various other antibiotics such as linezolid, vancomycin, or daptomycin are advocated in cases involving methicillin-resistant S. aureus. However, clindamycin remains the antibiotic of choice for necrotizing infections. Unlike penicillin, the efficacy of clindamycin is not affected by the inoculum size or stage of bacterial growth. It inhibits expression of the superantigen M-protein which one of the key factors in the pathophysiology of NSTIs. However, cases with resistance to clindamycin have been documented.,
We found Gram-negative rods Klebsiella and Bacteroides in the neck aspirate and a negative microbial culture and swabs of the chest lesion. The antibiotic sensitivity showed sensitivity to cotrimoxazole and levofloxacin. While Wüst  in his in vitro study showed the susceptibility of Bacteroides to cotrimoxazole, the susceptibility of Klebsiella to cotrimoxazole is under question due to several reports of resistance.,, In the present case, we used cotrimoxazole and maintained it for 3 weeks which proved to be effective.
While antibiotic therapy alone may be useful in mild cases, the thrombosis of the blood vessels may prevent antibiotics from reaching the site of infection in advanced cases. Hence, antibiotic therapy has to be combined with prompt and aggressive surgical debridement.
Even though CT is considered as the gold standard for diagnosis of NSTI, ultrasound and plain X-rays have also been found to be a useful tool in diagnosis, especially due to gas-forming bacteria. 17–57% of patients exhibit soft-tissue gas plain X-rays. The use of ultrasound evaluation is strongly recommended in patients with atypical or rapidly progressive cellulitis to detect NF at its early stage. In our case, the lack of a CT was compensated for, by plain radiographs and ultrasound to rule out the involvement of vital structures of the neck and the mediastinum.
Management of infections involves the contribution of a triad of factors: The host, the antibiotic and the surgical intervention. In an immunocompromised patient, early antibiotic therapy and surgical intervention become the key to resolving the infection. These patients frequently exhibit electrolyte and acid-base imbalances which must be addressed to prevent multi-organ dysfunction.
Following the surgery serial debridements; an average of three debridements spaced 12–36 h apart are needed to obtain control of gross infection.,, In our case, following the surgery, sequential debridements were carried out every alternate day with hydrogen peroxide and povidone iodine till fresh granulation was formed at the bed. A combination of povidone iodine, which has a broad-spectrum activity against bacteria and hydrogen peroxide, a weak acid with strong oxidizing properties, were found to be optimal. Ludwig's angina was treated with open surgical incision and drainage.
Following extensive surgical debridement, reconstruction, and skin coverage can pose tremendous problems. While simply allowing the wound to granulate may suffice, second-line soft tissue coverage should be considered. Our patient had been vetted for skin grafts 1 month after surgical debridement. However, due to financial reasons, he refused the surgery.
The overall mortality according to Elliot et al. for patients presenting with NTSI was 25.3%. However, the rate was a much higher 89% as noted by Urschel et al. for NF of the chest wall. They wrote that a delay or inadequacy of debridement were the main causes for the high mortality rates. Delay in diagnosis or surgery (mortality rate of 30%) and inadequate surgery (mortality of 50%) are also found to be major contributors to the increased mortality. Keung et al., in their multivariate analysis, found the absence of intraoperative bleeding, lower albumin level, systolic blood pressure, failure to initiate appropriate antibiotic therapy, older age, a higher international normalized ratio and American Society of Anesthesiologists physical status class to be associated with high mortality.
Anaya et al. created the first clinical score designed to predict death in patients with NSTI. It uses simple easily quantifiable variables. Our patient scored 3 on the mortality scale and mortality rate of 24% suggesting a grave prognosis [Table 4] and [Table 5].
Despite early and repeated extensive debridements, broad-spectrum antibiotics, monitoring in Intensive Care Units (ICU), and use of hyperbaric oxygen therapy (HBOT) some NF patients are “irretrievably sucked down the vortex of the cytokine cascade.” This suggests that there may be a role for antitoxin or immunomodulatory agents., The mortality for Ludwig's angina on the other hand, exceeded 50% in the preantibiotic era; it currently averages approximately 8% with antibiotic therapy, surgical drainage, and modern intensive care.
IV immunoglobulins (IVIGs) are being used in sepsis as they are assumed to neutralize streptococcal superantigen activity, thereby reducing plasma levels of TNF and IL-6. A 2013 cochrane review  noted that Kaul et al., studied the survival of patients treated with IVIG and found a survival rate of 67% versus 34% in the control group. IVIG, however, has not been Food and Drug Administration approved and its use and efficacy remain controversial. In the 2002 Cochrane review, the authors concluded that although a reduction in mortality among adults with sepsis was evident, this benefit was not seen in trials with low risk of bias. Large randomized clinical trials are required to provide reliable data.
The other available option is HBOT. HBOT increases tissue oxygen tension thereby salvaging critically ischemic areas. Furthermore, hyperoxia potentiates antibiotic efficiency and is anti-inflammatory. However, a recent Cochrane review failed to demonstrate the efficacy of HBOT as an adjunct for the treatment of patients with NF. Another factor to be considered is the transport of the patient out of the ICU and restricting acute care in a pressurized chamber.
Even though we did manage to save the patient, there were a large number of limitations. The diagnosis and pathogenesis was confusing due to the lack of a clear etiology. The main factor limiting us was the lack of resources to fund various diagnostic and surgical reconstructive procedures. The inability to obtain CT, Interferon gamma release assay for tuberculosis and polymerase chain reaction for varicella zoster virus was our main diagnostic setbacks. The accuracy of LRINEC score has not been confirmed in HIV patients, with one report concluding that immunocompromised patients had a lower LRINEC score but higher mortality rates. We also could not conclusively decide on the diagnosis of the first set of vesicles neither on the left side nor on the etiopathogenesis of the chest and neck diseases.
| Conclusion|| |
With the increased incidence of HIV, lethal illnesses such as NF and Ludwig's angina may occur from seemingly trivial causes. Both conditions present with systemic toxicity and rapidly spread through the fascial planes. Despite modern advances in medicine, NSTIs the same problems it did 200 years ago. The patient's survival depends on treatment without delay. Swift diagnosis and the need for an aggressive surgical treatment cannot be overemphasized.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]