A collection of individual cases

Cases involving gout, Guillain-Barr##eacute; syndrome, granulomatosis with polyangiitis, and others are discussed.


Case 1: An acute attack of extra-articular gout

By Radhika Ayyagari, MBBS, ACP Resident/Fellow Member, and Alejandro Moreno, MBBS, MPH, JD, FACP

The patient

A 35-year-old man with a medical history of gout, hypertension, and diabetes mellitus presented with a sudden, sharp, intense, nonradiating left groin pain 2 days prior to hospital admission. The pain minimally improved with nonsteroidal analgesics. There was no history of trauma, fever, dysuria, hematuria, urinary frequency, or gastrointestinal symptoms.

On examination, the patient was afebrile and in moderate distress from groin pain. The abdomen was not distended and bowel sounds were present, but there was tenderness over the left lower quadrant without rebound or guarding. The patient experienced pain over the left iliac fossa when he actively flexed the left hip from an extended position (a positive “psoas sign”) and there was decreased range of motion at the left hip, limited by pain. Rectal examination revealed exquisite tenderness over the left iliac fossa, and scrotal examination was normal without inguinal hernia. Femoral pulses were symmetric, and no bruits were audible.

Tless-thansubgreater-than2less-thanslashsubgreater-than weighted coronal views of the pelvis showing fluid collection around left psoas muscle arrows
T2 weighted coronal views of the pelvis showing fluid collection around left psoas muscle (arrows).

Laboratory examination revealed a mildly elevated white blood cell count of 12,800/µL (71% neutrophils). The serum uric acid level was 7.7 mg/dL (normal range, 2.6 to 7.2 mg/dL). MRI of the left hip showed tubular fluid collection with enhancement along the left iliopsoas and reactive external iliac lymphadenopathy (Figure 1).

The patient was admitted to the hospital for further evaluation of a possible psoas abscess and underwent CT-guided aspiration of the fluid collection. The fluid was cloudy and had 13,000 white blood cells/µL (56% neutrophils), and Gram stain and subsequent culture were negative. Further evaluation of the joint fluid aspirate revealed multiple negatively birefringent needle-shaped crystals under polarized light.

The patient was discharged home on indomethacin and allopurinol. He did well in follow-up, though he had another acute gout attack in the right knee 1 year later.

The diagnosis

This patient's diagnosis is an acute gout flare, manifested as an extra-articular fluid collection and associated pain from iliopsoas irritation. Acute gout classically affects the first metatarsophalangeal joints as inflammatory arthritis, but other small and large joints and bursae can be involved. The presence of negatively birefringent crystals in the synovial fluid confirms the diagnosis, as uric acid levels may be low during acute flares. Extra-articular, nonbursal gout usually presents as chronic tophi; acute extra-articular nonbursal gout flares are uncommon.

A review of the literature shows only a handful of case reports involving a wide variety of anatomical structures, including adipose tissue, brain, peripheral nerves, eyes, cartilages, tendons, and muscles. Treatment is similar to the intra-articular or bursal attacks: nonsteroidal anti-inflammatory drugs, steroids, and uricosuric agents. Uric acid-lowering therapy (ULT), such as allopurinol, should not be started during acute gout flares; however, such therapy should be continued in patients already taking these medications.

Pearls

  • An acute flare of gout must be considered in the differential diagnosis of painful intra-abdominal fluid collections, particularly in patients with a history of gout.
  • Acute extra-articular, nonbursal gout attacks can affect any organ of the body and are managed the same as intra-articular flares.

Case 2: Miller Fisher variant of Guillain-Barré syndrome

By Blake Haas, PhD, and Yenal Harper, MD, ACP Resident/Fellow Member

The patient

A 26-year-old man with no significant medical history presented with sudden-onset double vision. He was taking acetaminophen and pseudoephedrine for symptoms of a recent upper respiratory tract infection. He also reported perioral and bilateral fifth-finger paresthesias. Physical examination revealed bilateral esotropia, bilateral lateral rectus muscle weakness, and mydriasis. All other cranial nerves were without detectable abnormality, and a full neurological exam, including strength, sensation, reflexes, and gait, was normal. No skin lesions were noted.

An initial CT head and contrast MRI were unrevealing. Lumbar puncture revealed normal cerebrospinal fluid (CSF) glucose and protein without pleocytosis; oligoclonal bands were absent. MRI of the cervical and thoracic spine did not reveal any demyelinating lesions. On the fourth hospital day, his condition worsened: He developed unsteady gait and hyporeflexia of the upper and lower extremities. With the constellation of symptoms and findings, Miller Fisher syndrome (MFS) was suspected and therapy with intravenous immunoglobulin (IVIG) was given for 5 days. No steroids were given. Electromyography confirmed evidence of an acute motor polyneuropathy, and a positive serum GQ1b antibody was detected.

After 5 days of IVIG therapy, the patient's gait abnormalities improved, but ophthalmoplegia was still present. At subsequent outpatient follow-up, his gait imbalance had resolved and his diplopia had significantly improved.

The diagnosis

MFS is a rare variant of Guillain-Barré syndrome (GBS), which was described in 1956 as a constellation of ataxia, ophthalmoplegia, and areflexia. MFS accounts for approximately 5% of cases of GBS, itself a rare condition with an incidence of 1 to 2 in 100,000 patients. As with classic GBS, viral illness may precede Miller Fisher syndrome and other GBS variants, which supports autoimmunity (via molecular mimicry) as a possible cause.

Although MFS typically causes external ophthalmoplegia, internal ophthalmoplegia (as evidenced by loss of pupillary reflexes) may also be present. Motor conduction abnormalities may be present, but ascending sensory pathways are usually unaffected. Elevated CSF protein (“albuminocytologic dissociation”) is a common but not absolute finding in MFS and GBS. The serum GQ1b antibody against the ganglioside portion of peripheral nerves is positive in 85% to 90% of cases of MFS, whereas only approximately 20% of typical GBS cases test positive for this antibody.

Fortunately, MFS is often temporary, progressing for only a few weeks and often achieving full clinical recovery within 3 months. As with GBS, inpatient observation is required in patients presenting with MFS, which carries with it the risk of respiratory muscle failure. Treatment options shown to improve patient outcomes include IVIG or plasmapheresis, depending on the severity of illness and local culture of clinical practice. The use of steroids in MFS/GBS has not been shown to be beneficial, and steroids no longer have a role in management.

Pearls

  • Miller Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome (GBS) characterized by ataxia, ophthalmoplegia, and areflexia.
  • Treatment of MFS is similar as that for GBS and typically includes a combination of IV immunoglobulins and/or plasmapheresis depending on the severity of illness.

Case 3: Granulomatosis with polyangiitis

By Hamid Feiz, MD, ACP Member; Kristoff Naberezny, MD, ACP Member; Elana Oberstein, MD; Michael Lemont, MD; Natalya Lyubynska, MD, ACP Member; Shalini Kulkarni, MD, ACP Resident/Fellow Member; Rulz Cantave, MD, ACP Resident/Fellow Member; Kairavee Dave, MD, ACP Resident/Fellow Member; and Fulvia Banu, MD, ACP Resident/Fellow Member

The patient

Chest X-ray showing elevation of right side of the diaphragm
Chest X-ray showing elevation of right side of the diaphragm.
Diaphragm fluoroscopy showing the paralysis of the right diaphragm
Diaphragm fluoroscopy showing the paralysis of the right diaphragm.

A 67-year-old man presented with a 3-week history of shortness of breath, dry cough, and night sweats. He also reported recurrent episodes of purulent nasal discharge for 3 months. Physical examination revealed tenderness over the frontal and maxillary sinuses and dullness to percussion with decreased breath sounds at the right lung base. Chest radiograph showed right-sided hemi-diaphragm elevation (Figure 2), and subsequent diaphragm fluoroscopy was concerning for right phrenic nerve palsy (Figure 3).

Laboratory testing on admission revealed renal insufficiency (blood urea nitrogen level, 25 mg/dL; creatinine level, 1.7 mg/dL) and microscopic hematuria. The initial hospital course was noteworthy for new-onset lower-extremity numbness and tingling, epistaxis, and fever to 102 °F. Electromyography revealed bilateral amplitude reduction of sensory and muscle action potentials without alterations of conduction velocity, consistent with peripheral neuropathy. The erythrocyte sedimentation rate was 100 mm/h, and C-reactive protein level was 23.5 mg/L.

Two days into an extensive rheumatologic laboratory evaluation, this patient developed worsening dyspnea and hypoxia requiring intubation and mechanical ventilation. He was empirically treated with methylprednisolone, and 48 hours later, his hypoxemia and neurological symptoms improved and he was extubated. The previously noted phrenic nerve palsy also resolved with induction therapy. C-anti-neutrophil cytoplasmic antibody (c-ANCA) was positive at a titer of 1:60. Nasal biopsy ultimately showed evidence of granulomatous vasculitis.

The diagnosis

This patient's diagnosis is granulomatosis with polyangiitis (GPA, formerly “Wegener's granulomatosis”), a rare disease with a prevalence of 3 per million persons in the United States. There are 4 diagnostic criteria for GPA: abnormal urinary sediment (red cell casts or microhematuria), abnormal findings on chest X-ray (nodules, cavities, or fixed infiltrates), oral/nasal ulcers, and granulomatous inflammation on biopsy. GPA has a spectrum of clinical presentations that includes ear, nose, mouth, throat, and lung symptoms in over 90% of cases. Patients may present with nonspecific “flu-like” symptoms, weight loss, cutaneous vasculitis, arthritis, and peripheral neuropathy. Mononeuritis multiplex, foot drop, or wrist drop may be the sole initial finding. Phrenic nerve palsy is not a typical feature.

GPA should be suspected in the presence of elevated inflammatory markers along with signs and symptoms of vasculitis and characteristic organ system involvement. Although a positive c-ANCA is highly suggestive of GPA, definitive diagnosis is made histologically upon biopsy of affected tissue.

Patients with life- or organ-threatening manifestations (e.g., rapidly progressive glomerulonephritis, alveolar hemorrhage, or mononeuritis multiplex with motor involvement) require immediate hospitalization and treatment with high-dose immunomodulators (usually corticosteroids with or without cyclophosphamide) to induce remission. Corticosteroids, along with methotrexate or azathioprine, are used to induce and maintain remission in less severe cases.

GPA is a relapsing condition, with 10-year relapse rates as high as 67% in some series. Causes of death vary depending on the population studied, but death is most often reported from GPA-related lung disease and kidney failure, as well as complications of immunosuppressive treatment and increased rates of cardiovascular events.

Pearls

  • Granulomatosis with polyangiitis (GPA, formerly “Wegener's granulomatosis”) is an autoimmune disorder that often presents with nonspecific symptoms; the classic clinical pattern is a triad involving the upper airway, lungs, and kidneys, but peripheral nerves can also be affected.
  • When GPA is clinically suspected, prompt consideration of intravenous glucocorticoids is necessary to prevent potentially fatal complications.

Case 4: Drug reaction with eosinophilia and systemic symptoms

By Nureddin Almaddah, MD, ACP Resident/Fellow Member; Elizabeth George, MD; Meenakshi Kundi, MD, ACP Resident/Fellow Member; and Arooj Hyat, MD

The patient

Generalized erythematous macular lesions with regions of confluence involving the right upper extremity extending to the dorsal surface of the hand
Generalized erythematous macular lesions, with regions of confluence, involving the right upper extremity, extending to the dorsal surface of the hand.
Bilateral lower extremities reveal confluent areas of erythema prominent in the distal thigh ankle and dorsal surface of the foot
Bilateral lower extremities reveal confluent areas of erythema prominent in the distal thigh, ankle, and dorsal surface of the foot.

An 81-year-old woman with a history of chronic obstructive pulmonary disease and diabetes presented with 3 days of rash and fever. She was recently admitted with right ankle septic arthritis and received 4 weeks of intravenous ceftriaxone and vancomycin; her course was subsequently complicated by Clostridium difficile infection. On examination, the patient was febrile (temperature 102.9 °F), tachycardic, and tachypneic but normotensive and saturating normally on room air. Her skin was notable for a maculopapular erythematous rash over the trunk and extremities, no vesicles or pustules formation, and no involvement of mucous membranes (Figure 4 and Figure 5).

Laboratory studies were remarkable for the following: a leukocytosis of 23,000 cells/µL, with 13% bands and 10% eosinophils; acute kidney injury, with a serum creatinine level of 2.3 mg/dL (normal baseline); and urinalysis with pyuria and microscopic hematuria but no bacteruria. Aminotransferase levels at admission were normal but subsequently became elevated (aspartate aminotransferase level, 276 U/L; alanine aminotransferase level, 502 U/L). A skin biopsy was obtained, after which empiric treatment with intravenous corticosteroids was initiated.

Skin biopsy of the upper extremity demonstrating epidermal spongiosis with patchy lymphocyte exocytosis white arrow and a superficial perivascular and interstitial lymphocytic inflammatory infiltrat
Skin biopsy of the upper extremity demonstrating epidermal spongiosis with patchy lymphocyte exocytosis (white arrow) and a superficial perivascular and interstitial lymphocytic inflammatory infiltrate (black arrows) with numerous eosinophils and mild dermal edema.

The patient had a dramatic response to steroids, with rapid improvement of rash and kidney function and resolution of peripheral eosinophilia. The biopsy showed spongiotic and superficial perivascular dermatitis with numerous eosinophils (Figure 6), confirming the diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS). The culprit medication in this case was ultimately not definitively identified.

The diagnosis

DRESS is a potentially life-threatening adverse drug reaction, with an estimated mortality rate of approximately 10%. It was originally observed in patients treated with anticonvulsants in the early 1930s. Numerous drugs, including sulfonamides and sulfasalazine, have been reported to cause the DRESS syndrome, but anticonvulsants such as phenobarbital, carbamazepine, and phenytoin are the most common. DRESS presents with cutaneous manifestations and internal organ involvement approximately 2 to 6 weeks after exposure to the causative medication.

The hallmark clinical features of DRESS are eosinophilia, rash, hepatitis, and a compatible medication history (exposure to drugs known to cause DRESS). There is a diversity of cutaneous eruption and organs involved. The most commonly encountered dermatologic manifestation of DRESS syndrome is an erythematous morbilliform rash, and the most commonly affected organs are the liver and kidneys. Early recognition of DRESS and immediate immunosuppressive treatment, along with immediate cessation of all potential culprit medications, are critical to prevent a potentially fatal outcome.

Pearls

  • Drug reaction with eosinophilia and systemic symptoms (DRESS) is a life-threatening process characterized by a rash, peripheral eosinophilia, and liver test abnormalities approximately 2 to 6 weeks after exposure to a causative medication.
  • Management of DRESS includes early recognition, immunosuppressive therapy, and cessation of suspected culprit medications.

Case 5: Cannabinoid hyperemesis syndrome

By Robert C. Kornas, MD, ACP Resident/Fellow Member, and Suelyn Boucree, MD, ACP Member

The patient

A 19-year-old woman was admitted to the hospital reporting severe nausea, vomiting, and abdominal pain for 1 day. She reported as many as 70 episodes of nonbilious, nonbloody vomiting and retching over the course of 24 hours with severe, diffuse abdominal pain and anorexia. She reported no fever, chills, or diarrhea and had no recent travel or sick contacts. She revealed that she was a heavy cannabis user, smoking at least 2 to 3 g of marijuana daily for 4 years.

Two hours prior to the onset of her symptoms, she smoked 2 g of marijuana. When asked about relieving symptoms, she stated that she had taken at least twelve 45-minute hot showers, which temporarily resolved her symptoms. After completing her bathing routine, the symptom severity resumed. Her physical examination was remarkable for generalized abdominal pain, dry mucous membranes, and mild tachycardia. Laboratory examination was unremarkable, and she was not pregnant. Her HbA1c was 5.7%. Her urine drug screen was positive for only cannabinoids.

The patient was successfully volume-resuscitated, and her symptoms resolved. She was discharged with instructions to avoid marijuana but returned 12 days later with the same symptoms after smoking 1 g of marijuana. An extensive repetitive evaluation was avoided, and the patient was treated symptomatically. She subsequently successfully ceased using marijuana and has remained symptom-free without further spells of intractable emesis.

The diagnosis

The patient was diagnosed with cannabinoid hyperemesis syndrome (CHS). CHS is characterized by cyclical nausea, vomiting, and abdominal pain following heavy and chronic marijuana use. Although the exact mechanism of CHS is unknown, the long half-life of marijuana, in addition to its lipophilic properties, may delay gastric emptying and motility, leading to symptoms. Temporary relief of symptoms by taking prolonged hot baths or showers is a commonly utilized means of symptom alleviation in patients with CHS. The proposed mechanism is linked to the endocannabinoid effect on the hypothalamus-pituitary-adrenal system, in which the thermosensory input from the hot water provides peripheral cutaneous stimulation and eventual relief.

Most patients are daily users of marijuana for years or even decades before the sudden onset of symptoms. Patients are typically symptomatic for 24 to 48 hours before symptoms gradually resolve with supportive care and conservative management. Cessation of marijuana use is the only known method to prevent future occurrences.

The key factor in making the appropriate diagnosis is asking detailed questions about the patient's social history with careful attention to the frequency and amount of marijuana use and bathing habits. Often missed or only briefly discussed during patient interviews, details about marijuana use can aid the clinician in making the correct diagnosis of CHS and allow for avoidance of an extensive and costly evaluation.

Pearls

  • Cannabinoid hyperemesis syndrome (CHS) is characterized by cyclical nausea, vomiting, and abdominal pain following heavy and chronic marijuana use, often reported to be relieved by taking hot baths or showers.
  • Conservative management and supportive care are often the only treatments needed before symptoms gradually improve within 24 to 48 hours; complete cessation of marijuana use is the only known way to avoid future recurrences of CHS.