Case 1: Diabetic neuropathic foot arthropathy (Charcot foot)
By Stephanie V. Sherman, MD
A 37-year-old woman presented with four weeks of progressive pain, redness, and swelling in her left foot. She works and spends most of the day on her feet but had not experienced recent foot trauma or ulcers. She had no fevers, chills, arthritis, or myalgias but did have painful paresthesias in both feet. Her medical history included hypertension and poorly controlled type 2 diabetes (HbA1c, 13%).
On presentation, her temperature was 98.8 °F, her blood pressure was 149/104 mm Hg, and her heart rate was 97 beats/min. Her left foot had a flat arch with lateral deviation of the forefoot. The foot was warm, red, and swollen when compared to the right. There was no tenderness, ulceration, or limited range of motion at the ankle. She had onychomycosis and decreased proprioception. Labs showed a normal white blood cell count, erythrocyte sedimentation rate (ESR) of 26 mm/h (normal <20 mm/h), high-sensitivity C-reactive protein level of 0.478 mg/dL (normal <0.3 mg/dL), and negative blood cultures. Plain radiography of the foot showed lateral displacement of the metatarsals with erosion of the proximal second and third metatarsals, concerning for osteomyelitis (Figure 1). An MRI showed increased T2 signal in all tarsal and metatarsal bones with associated soft-tissue edema, also consistent with osteomyelitis. The patient declined immediate foot amputation and instead underwent bone biopsy, which showed normal bone with negative cultures. Ultimately, she was treated conservatively with immobilization and an off-loading shoe.
Diabetic neuropathic foot arthropathy (Charcot foot) is a noninfectious complication of diabetic neuropathy in which loss of proprioception results in changes in weight-bearing that lead to chronic, progressive bony destruction. Charcot foot can present acutely with warmth, erythema, and induration, thus mimicking common conditions such as soft-tissue infection, septic arthritis, gout, or osteomyelitis. On physical exam, Charcot foot often presents with soft-tissue inflammation and distorted bony architecture such as metatarsal deviation and collapsed arch. Pinprick and position sensation are typically reduced while pulses are preserved. Foot ulcers may be present, though their absence significantly lowers the likelihood of osteomyelitis as the cause of bone destruction. In Charcot foot, laboratory markers of inflammation, such as peripheral white blood cell count and ESR, are typically normal.
Although imaging is commonly used to work up diabetic foot symptoms, results may not easily differentiate Charcot foot from osteomyelitis. Both Charcot foot and osteomyelitis can lead to periosteal reactions and bone erosion on plain radiograph; on MRI, both diagnoses are associated with abnormal bone marrow signal, cortical disruption, and adjacent soft-tissue inflammation. Radiographic features that support the diagnosis of Charcot foot include involvement of the midfoot (instead of toe, forefoot, or heel in osteomyelitis) and presence of joint subluxations or dislocations. If the diagnosis remains equivocal after consultation with a radiologist, a bone biopsy can be performed to rule out osteomyelitis, although it is not required to diagnose Charcot foot.
- Charcot foot (diabetic neuropathic foot arthropathy) can present acutely with pain, redness, and swelling.
- Charcot foot can be challenging to differentiate from osteomyelitis clinically and on commonly ordered imaging studies; normal inflammatory markers and joint or arch deformities can help distinguish this condition from other diabetic foot complications.
Case 2: Acute bacterial prostatitis
By Zaven Sargsyan, MD
A 61-year-old man with type 2 diabetes was admitted with two days of hematuria and fever. Ten days prior to admission, he was treated for new urinary retention, which was attributed to prostatic hypertrophy and the use of diphenhydramine for allergies. An indwelling urinary catheter was placed, and he was started on tamsulosin. One week later, he began to experience malaise, chills, dysuria, and intermittent bleeding into his urinary catheter bag. On examination, he was febrile, tachycardic, and tender over the left lower and suprapubic abdomen. There was no costovertebral angle tenderness. His catheter was draining cloudy, pink-tinged urine. The rectal exam was deferred. Treatment with intravenous fluids and cephalosporin antibiotics was initiated. Serum laboratory values were notable for a white blood cell count of 21,000 cells/µL. Urinalysis showed 148 white blood cells and 89 red blood cells per high-power field, but no nitrites. The urine culture grew Serratia marcescens susceptible to both cephalosporins and fluoroquinolones; blood cultures were sterile. Over the next three days, while receiving a cephalosporin antibiotic, the patient's leukocytosis and tachycardia improved, but he continued to have malaise and intermittent fevers. A CT of the abdomen was performed, showing no nephrolithiasis, unremarkable kidneys, and a moderately enlarged prostate with heterogeneous contrast enhancement. The serum prostate-specific antigen (PSA) level was elevated at 76 ng/mL (normal <4 ng/mL). Antibiotic therapy was changed to ciprofloxacin, after which the patient rapidly defervesced. After a 6-week course of antibiotics was completed, the PSA normalized.
Acute bacterial prostatitis is rare and a challenge to distinguish from a simple urinary tract infection. Enteric gram-negative bacilli are the most common culprits and are thought to infiltrate the gland through intraprostatic urinary reflux. Major risk factors include anatomic abnormalities such as urinary retention or instrumentation and immunocompromised states such as diabetes mellitus. Prostatitis should be suspected in men with urinary tract infections who exhibit signs of sepsis but do not have apparent pyelonephritis or obstructive nephrolithiasis. Acute urinary retention, transient elevation in PSA, and gland enlargement and hyperemia on imaging can support the diagnosis. A digital rectal exam may also be helpful by demonstrating “bogginess” and tenderness of the gland, but vigorous massage should be avoided, as it may precipitate bacteremia.
Recognizing prostatic involvement in a lower urinary tract infection is important for several reasons. Acute prostatitis is potentially life-threatening, resulting in bacteremia in up to 25% of cases. Inadequate response to antibiotics can necessitate surgical drainage of prostatic abscesses. The treatment of bacterial prostatitis requires appropriate antibiotic selection for prostatic tissue penetration. Fluoroquinolones and trimethoprim-sulfamethoxazole have better penetration than many beta-lactams or carbapenems and are favored by most experts when culture data are available. In the acutely ill patient, however, the initial antibiotic choice should be informed by susceptibility patterns of Enterobacteriaceae locally or from the individual's past specimens.
- Consider acute bacterial prostatitis when urinary tract infections lead to sepsis or acute urinary retention in men, particularly in those with prostatic hypertrophy and diabetes mellitus.
- Fluoroquinolones and trimethoprim-sulfamethoxazole have superior prostatic penetration and should be used to treat bacterial prostatitis, especially if culture data and sensitivity information are available.
Case 3: Tuberculous peritonitis
By Krishna Sajja, MD, and Lubna Khawaja, MD
A 35-year-old woman from Guatemala presented with three months of abdominal swelling. She had associated symptoms including anorexia, night sweats, and nonbloody, nonbilious vomiting, but no fevers, cough, hemoptysis, alcohol use, or recent travel. She was afebrile with a heart rate of 115 beats/min and blood pressure of 100/40 mm Hg. On examination, she had a distended and diffusely tender abdomen with a positive fluid wave. Labs showed leukocytosis with neutrophil predominance. Viral hepatitis panel and pregnancy test were unremarkable, and interferon-gamma release assay (IGRA) was indeterminate. CA-125 level was elevated to 800 units/mL (normal range, 0 to 35 units/mL). A right upper quadrant ultrasound revealed portal vein thrombosis and ascites. Paracentesis showed 475 white blood cells/µL with 89% lymphocytes, low serum-ascites albumin gradient (SAAG), negative cultures, and negative cytology. Abdominal CT and MRI showed omental nodularity with normal ovaries, and panendoscopy was unrevealing. The patient underwent an exploratory laparoscopy that demonstrated peritoneal nodules and friable omental tissue with adhesions (Figure 2).
Biopsies revealed noncaseating granulomas (Figure 3) with negative acid-fast bacilli (AFB) stain and culture. Repeat IGRA testing was positive. Therapy for Mycobacterium tuberculosis with rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) was initiated, but the patient was ultimately lost to follow-up.
Tuberculous peritonitis (TBP) accounts for less than 1% of all forms of Mycobacterium tuberculosis (MTB) infection, but it is the most common form of gastrointestinal MTB. Infection occurs most commonly due to reactivation of latent tuberculosis peritoneal foci that were established during primary lung infection via hematogenous spread. Risk factors include residence in endemic MTB regions, alcoholic liver disease, peritoneal dialysis, anti-tumor necrosis factor drug therapy, diabetes, and HIV infection. TBP presents with nonspecific symptoms including fevers, weight loss, anorexia, nausea, vomiting, abdominal pain, diarrhea, constipation, and abdominal swelling. Portal vein thrombosis is a rare but documented manifestation. Concurrent lung involvement may be present, although 80% of gastrointestinal MTB infection occurs in the absence of active pulmonary disease.
The diagnosis of TBP is challenging given its insidious onset and variable presentation; TBP should, however, be considered in all patients with lymphocytic ascites with a low SAAG. This young woman's elevated CA-125 level made ovarian cancer a consideration, but this marker can also be elevated in TBP and thus often confounds the diagnosis. TB studies and laparoscopy form the basis of diagnosis. While the purified protein derivative (PPD) test is not helpful in the diagnosis of active MTB infection, IGRA testing has greater than 90% sensitivity and specificity in the diagnosis of acute TBP. Ascitic AFB smear testing is positive in fewer than 3% of fluid samples. While polymerase chain testing for MTB is only useful for AFB smear-positive ascites samples, fluid cultures are positive in approximately one-third of cases. Elevated adenosine deaminase (ADA) levels in ascitic fluid additionally aid in diagnosis, given high sensitivity (93%) and specificity (96%). Laparoscopy also has excellent sensitivity (93%) and specificity (98%) when macroscopic appearance and histology findings are combined. Although MTB is classically associated with caseating granulomas, noncaseating granulomas can also be seen in biopsy of infected tissue.
- Gastrointestinal tuberculosis infection, specifically TBP, should be considered in the differential diagnosis in patients with unexplained low SAAG ascites and risk factors for MTB infection.
- Adenosine deaminase levels in ascites may assist in diagnosis, but laparoscopy with tissue biopsy should be considered in all patients with possible TBP to avoid delays in diagnosis and treatment.
Case 4: Unilateral lower-extremity edema as a sign of gynecologic malignancy
By Priti Dangayach, MD, ACP Member
A 61-year-old woman presented to her outpatient physician with erythema and swelling of the right lower leg. She reported no fever, chills, trauma, travel, prolonged immobilization, chest pain, shortness of breath, paroxysmal nocturnal dyspnea, or abdominal swelling. Outpatient evaluation consisted of a lower-extremity ultrasound, which was negative for deep venous thrombosis, and a CT of the extremity that showed nonspecific soft-tissue swelling. Despite a course of antibiotics for presumed cellulitis, the erythema worsened, and she was admitted for antibiotic “failure” and intravenous therapy. On hospital presentation, she had normal vital signs. Her right leg was swollen and erythematous with increased thigh girth compared to the left; her left leg appeared normal (Figure 4). Nontender right inguinal lymphadenopathy was present.
Further history revealed a diagnosis of stage I uterine adenocarcinoma six years prior, treated with hysterectomy and bilateral salpingo-oophorectomy. A CT of the pelvis showed significant right iliac chain lymphadenopathy causing right external iliac vein compression (Figure 5). Lymph node core needle biopsy revealed metastatic poorly differentiated carcinoma. She underwent stenting of the right external iliac vein and peritoneal debulking, which revealed endometrial adenocarcinoma with lymphovascular invasion.
This patient's unilateral leg swelling resulted from malignant lymph nodes compressing the external iliac vein in the setting of uterine adenocarcinoma recurrence. Endometrial cancer is the most common gynecologic malignancy in the United States with more than 60,000 new cases per year. It has an approximate 15% overall rate of relapse, most often within three years of initial diagnosis. Presenting signs of localized relapse include vaginal bleeding, pelvic pain, and constitutional symptoms. Usual sites of recurrence are the vagina, pelvic and para-aortic lymph nodes, peritoneum, and lung. In the pelvic region, lymphangitic spread is most commonly seen to the external iliac lymph nodes followed by obturator and common iliac nodes. While lower-extremity swelling from venous obstruction in metastatic gynecological cancers has been described, this type of swelling may be mistakenly attributed to secondary lymphedema. Venous obstruction can be amenable to stent placement, which can alleviate the obstruction, increase mobility, and improve quality of life.
Unilateral lower-extremity edema warrants further evaluation of the underlying cause, with consideration of soft-tissue, vascular, and lymphatic pathologies. Soft-tissue causes of unilateral edema include infections and compartment syndrome. Disruptions in the venous drainage system from deep venous thrombosis or prior vein stripping can also result in unilateral edema. Unilateral edema secondary to lymphatic obstruction can be seen with surgery, malignancy, radiation-induced scarring, recurrent infections, lymphatic hypoplasia, and filariasis. Bilateral swelling may be asymmetric due to physiologic compression of the left iliac vein by the right iliac artery or prior vascular or lymphatic injury to the lower extremity.
- Inguinal lymphadenopathy may be the initial presentation for an occult malignancy, especially with gynecologic cancers that develop lymphangitic spread to the external iliac, obturator, and common iliac lymph nodes.
- Unilateral lower-extremity edema has a variety of causes, including venous obstruction, and may potentially be alleviated by stent placement.