TUBERCULOSIS (TB) is one of the oldest diseases known to humankind, hypothesized by scientists to have originated more than 150 million years ago (Barberis, Bragazzi, Galluzzo, & Martini, 2017). Robert Koch discovered the causative agent, Mycobacterium tuberculosis, in 1882 (Varshney & Goyal, 2011). The disease currently affects 2 billion people worldwide, with approximately 10.4 million new cases per year (Barberis et al., 2017). The majority of clinical cases are pulmonary TB. Clinical signs and symptoms include hemoptysis, weight loss, anorexia, fever, lethargy, persistent cough, lymphadenopathy, and night sweats. Like systemic TB, the cutaneous variant has many clinical variations and prognoses. Clinical signs and symptoms for cutaneous TB (CTB) may include joint pain, lymphadenopathy, and painful nodular lesions. They may or may not have any of the pulmonary symptoms included earlier. Cutaneous TB continues to be one of the most difficult diagnoses to make because of the wide variations in its clinical appearance, histopathology, immunology, and treatment response. Cutaneous TB accounts for only 1.5% of all cases of extrapulmonary TB and 0.15% of all cases of skin infectious skin diseases worldwide (Van Zyl, du Plessis, & Viljoen, 2015). Cutaneous TB has several clinical manifestations (see Appendix Table A1).
The prevalence of this disease has increased in the 21st century due to a high incidence of the human immunodeficiency virus (HIV) infection and multidrug-resistant (MDR) pulmonary TB. HIV infection, diabetes mellitus, and other autoimmune deficiencies decrease cure rates, increase mortality, and increase the incidence of MDR pulmonary TB (Varshney & Goyal, 2011). Tuberculosis is the most virulent opportunistic pathogen worldwide for patients living with HIV (World Health Organization [WHO], 2017). There were at least 300,000 deaths from HIV-associated TB; this accounts for 32% of acquired immunodeficiency syndrome (AIDS) deaths (WHO, 2017). The majority of deaths (84%) took place in Africa (WHO, 2017).
What is the clinical significance of remaining up to date on TB education as an emergency medicine provider? Emergency medicine providers encounter a significant number of high-risk individuals, including those who have traveled to/moved from TB endemic regions, are immunocompromised, live in low-income areas, and/or are incarcerated. This case documents a rare clinical manifestation of CTB seen in an emergency department in Gonaives, Haiti, in 2016. HIV rates in Haiti are similar to those of the United States, with 2.1% of the population in Haiti and 2.4% of the population in the United States being known to be HIV-positive (Chepkemoi, 2019).
CASE 1: HISTORY OF PRESENT ILLNESS
A 32-year-old Haitian woman presented to the emergency department with generalized weakness, weight loss, night sweats, intermittent fevers, and several lesions varying from 1 to 3 cm in diameter on her face, right neck, upper back, and right arm. The patient stated that she had soft nontender lumps that had progressively grown in size over the past 2 months. They burst open with purulent drainage and were now very painful. She denied chest pain, shortness of breath, wheezing, productive cough, hemoptysis, and syncope. The patient worked part-time in a bank and had no past medical history apart from childbirth. Gravida: 8; term: 5; para: 2; abortus: 1; living: 5. One child died before the age of 5 years, not including the spontaneous abortion and the premature baby who died in infancy. She stated that her remaining five children were healthy. The patient reported that she had been sexually active with two male partners in the past year and denied the utilization of a barrier contraception.
Case 1: Vital Signs
- The patient's vital signs were as follows:
- Temperature: 37.4 °C
- Oxygen saturation: 88%
- Heart rate: 105
- Blood pressure: 95/63
- Pain: 4/10 at sites of lesions
Case 1: Physical Assessment
The physical assessment of Case 1 yielded the following observations and assessments:
- General: The patient was a thin, cachectic female. A&0 × 4. The patient appeared malnourished with muscle wasting but was in no apparent distress.
- HEENT: Tender bilateral anterior and posterior cervical lymphadenopathy, bilateral axillary lymphadenopathy. Head normal cephalic, smooth, symmetrical, w/o swelling, tenderness; with teeth clench strong and equal; OP moist and pink w/o lesions or exudates. PERRLA, trachea midline, neck supple. Nasal turbinates pink and symmetrical bilaterally. Zero tonsils.
- Respiratory: Clear to auscultation bilaterally, no rales, rhonchi, pleural rubs, or stridor noted. Chest expansion equal bilaterally.
- Cardiovascular: RRR, normal S1, S2, no murmurs, no gallops or rubs. No edema or cyanosis.
- MS: 5/5 strength equal bilaterally in upper and lower extremities, sensation equal bilaterally, no erythema noted, no edema noted, +2 radial and pedal pulses. The patient was able to bear weight and ambulate with a steady gait and without pain.
- Neuro: Followed commands appropriately. Cranial nerves II–XII intact. Good muscle bulk and tone. Strength 5/5 bilateral upper extremities (BUE) and bilateral upper extremities (BLE). Grip strength 5/5 BUE. Finger to nose, heel to shin, intact. Gait steady.
- Skin: Several lesions varying from 1 to 3 cm in diameter on the face, right neck, upper back, and right arm × 2 months. Tender ulcerative lesions with draining sinuses. The center of the wound contained granulomas tissue and was oozing a moderate amount of purulent and serosanguineous drainage. Lesions were surrounded by a blue-tinged border that was not blanchable on several of the more advanced lesions. Fistula noted to the right upper back (along the inner border of right scapula) that tunneled approximately 4 cm under a ridge of blue nonblanchable skin. No induration or rash noted. Skin was otherwise clean, dry, and intact. Hair was clean and well kept, normal female hair distribution (see Appendix Figures A1 and A2).
- Psychiatric: Patient was calm and cooperative.
It can be challenging to differentiate between the various forms of CTB. When entertaining different conditions for a differential diagnosis, this chart can be a helpful tool, as each type of CTB manifests differently.
For this specific case, here are the differential diagnoses to consider (see Appendix Table A2).
- HIV infection
- Metastatic TB abscesses (tuberculous gumma)
- Syphilitic gumma
- Deep fungal infections
- Pyoderma gangrenosum
Initial laboratory evaluation
- Mantoux tuberculin skin test (TST): Weakly positive for Mycobacterium tuberculosis at 7-mm induration
- Sputum culture (induced) (×3)
- Bacterial culture: Normal bacterial flora, negative for Streptococcus pneumoniae, Klebsiella pneumoniae, Staphylococcus aureus, and Escherichia coli
- AFB stain: Moderately positive—1+ (1–9/100 fields)—numerous acid-fast bacilli (×3)
- Polymerase chain reaction (PCR) positive for Mycobacterium tuberculosis, susceptible for isoniazid, rifampin, ethambutol, and pyrazinamide (×3)
- Wound Culture PCR (Löwenstein medium): Purulent drainage positive for M. TB. The determination of lymphocytic subpopulations (CD3, CD4, CD4, and coefficients) revealed no alterations. Antibiogram tests showed that the strain was sensitive to all the anti-TB drugs.
- Skin biopsy: Suppurative tuberculoid granulomas, tubercle bacilli, copious numbers of organisms, areas of wedge-shaped caseous necrosis
- Chest radiograph: Diffuse consolidation and fibrosis present in the left and right upper lobes. Computed tomographic (CT) scan recommended
- CT scan: Diffuse and ill-defined pneumonitis
- Complete blood cell (CBC) count:
- White blood cells (WBCs): 8.34 × 109/L (4–11 × 109/L)
- Red blood cells (RBCs): 4.89 × 106/L (4.7–6.1 × 106/L)
- Hemoglobin (Hb): 8.8 g/dl (12–15.5 g/dl)
- Hematocrit (Hct): 38% (42%–52%)
- Neutrophil: 2.01 (1.5–8 × 109/L)
- Total leukocytes: 14 × 109/L (4–11 × 109/L)
- Eosinophil: 0.6 × 109/L (0–6 × 109/L)
- Erythrocyte sedimentation rate (ESR): 37 mm/hr (0–20 mm/hr)
- C-reactive protein (CRP): 15.3 mg/L (less than 10 mg/dl)
- Neutrophil to lymphocyte ratio (NLR): 7.1 (1–3)
- Comprehensive metabolic panel (CMP): Within normal limits
- Rapid plasma regain (RPR): Negative
- Rapid HIV antibody test: Positive
- CD4 count: 350 cells/ml
- Quantitative HIV RNA: 56,232 copies/ml
- HCV viral load: 182,473 units/ml
- Blood cultures ×2, 5 min apart: Negative
- Disseminated hematogenous TB (tuberculous gumma and pulmonary TB)
- HIV infection
There are three main subtypes of tuberculids, a group of cutaneous skin diseases that demonstrate hypersensitivity reactions to TB antigens. These include papulonecrotic tuberculids, lichen scrofulosorum, and erythema induratum of Bazin (Handog & Macarayo, 2019). Mycobacterium tuberculosis, M. bovis, and the BCG vaccine can all cause CTB (Marco, Solé, Raguer, & Aranda, 2014). There are several findings that support diagnosis of a tuberculid, including failure to detect Mycobacterium tuberculosis in stains or cultures of affected tissue, frequent resolution of skin lesions with anti-TB therapy, a strongly positive TST, a positive interferon-γ release assay, presence of an endogenous TB infection, and granulomatous tissue present in histopathology. Cutaneous TB can occur either from the spread of TB from an endogenous origin or from the entry of mycobacteria into the skin. The host's immune response to mycobacteria is an important factor. Although rare, TB abscesses have been documented months after receiving the BCG vaccination (Marco et al., 2014). Cold abscesses or gummas are a result of metastatic spread of mycobacteria from the blood (Marco et al., 2014). The abscesses typically form in the limbs or the trunk and spare the deeper tissues (Macgregor, 1995). Metastatic TB abscesses point to poor prognosis in immunosuppressed and malnourished individuals (Macgregor, 1995). Even with treatment, spontaneous lesions can persist and self-resolve for years (Centers for Disease Control and Prevention [CDC], 2016a). If lesions become necrotic, they must be surgically excised (CDC, 2016a).
The patient was transferred to a higher acuity hospital in Port-au-Prince, Haiti. The patient had the tuberculous gummas surgically irrigated and debrided and all necrotic tissue was removed. There was concern for secondary bacterial infection, so the patient was treated with Bactrim DS 1 tablet twice a day for 14 days. The patient was placed on an intensive phase of rifampin, isoniazid, pyrazinamide, and ethambutol daily for 56 doses (CDC, 2016a) and subsequently placed on a continuation phase of rifampin and isoniazid daily for 126 doses (CDC, 2016a). All doses administered were directly observed and documented by a health care professional. Specimens were obtained at monthly intervals until two negative specimens were obtained (CDC, 2017b, 2017c). At the time of her hospitalization, due to cost and availability, there was no access to antiretroviral therapy in Port-au-Prince, Haiti. Although she was unable to be treated for her HIV infection, she was placed on a list should the treatment regimen become available in the future (see Appendix Table A2, CDC, 2016b; Table A3, Frankel, Penrose, & Emer, 2009; Table A4, Frankel et al., 2009; and Table A5).
OUTCOME, FOLLOW-UP, COMPLICATIONS, AND PROGNOSIS
The patient's condition improved moderately as a result of treatment. Her subcutaneous lesions cleared over the period of several months, and she healed well from the incision and drainage. Because she had a positive sputum culture, specimens were obtained monthly until two consecutive negative cultures were obtained. The patient finished the duration of her TB intensive and continuation phase. Her chest radiographs showed improvement over time; however, some pulmonary fibrosis remained. To have optimal outcomes, the patient would need to receive treatment of HIV infection. Unfortunately, she has not had access to antiretroviral therapy and may never have the opportunity to receive it in her lifetime (see Appendix Table A6).
Although this case summarized a rare form of CTB in an emergency department in Haiti, both pulmonary TB and CTB are relevant to care administered in the emergency department in the United States. There were 9,105 cases of TB per 100,000 people living in the United States in 2017 and that number has remained consistent for the past 9 years (CDC, 2017a). Pulmonary disease, either exclusively or in combination with extrapulmonary disease, represents the majority of cases in the United States at 79.2% (CDC, 2017a). The remainder of the cases are solely extrapulmonary at 20.8% (CDC, 2017a). In the United States, there were 1,887 cases of extrapulmonary TB with 2,011 body sites (CDC, 2017a). HIV co-infection rates in the United States are at 9.2% for patients 25–44 years of age and 5.5% for patients of all ages (CDC, 2017a).
As emergency medicine providers, it is essential to be up to date on current practice guidelines for TB patients including modifications for immunocompromised and high-risk patients. It is also vital to rule out forms of CTB that are immediately life-threatening such as miliary/meningeal TB and patients can decompensate rapidly. With the increase in accessibility to travel to or from TB endemic countries, it is easier to contract and/or spread TB. There is high probability that patients with both pulmonary and extrapulmonary TBs will present to many emergency departments. Cutaneous TB should be considered in patients with atypical skin lesions that appear to be mycobacterial in nature. Infectious disease providers should be consulted promptly. With thorough assessment skills, essential diagnostics, and proper medication management, most patients have favorable outcomes. State/federal treatment guidelines must be adhered to while developing treatment regimen. Social determinants of health, patient resources, and access to care should always be considered.
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