Introduction

Rheumatic diseases can have a wide range of clinical presentations involving multiple anatomical regions, including the joints, skin, lungs, eyes, and nervous system. Because many of these diseases are complex and other conditions, such as infection, can mimic rheumatologic illness, providers need to consider certain key items when developing a differential diagnosis and performing a diagnostic workup, in order to arrive at the correct diagnosis. The following cases highlight several don't-miss findings or diagnostic tests for rheumatologists or other healthcare providers across a variety of disease presentations.

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Erythema Multiforme-like Rash in Lupus

A 47-year-old woman presented with an expanding red, itchy rash with some areas of blistering. Her blood work showed antinuclear antibody (ANA) positivity in a speckled pattern, and anti–SS-A positivity. She was not currently taking medications. Serum studies for acute infection with Epstein-Barr virus, cytomegalovirus, and herpes simplex were negative. Skin biopsy showed destructive interface dermatitis and epithelial cell necrosis.

These findings were consistent with lupus leading to an erythema multiforme-like disease that has been termed "Rowell syndrome." The patient improved with oral and topical steroid therapy and hydroxychloroquine.

Take-home points:

• Erythema multiforme-like lesions may occur in lupus.
• Consider medications and certain infections in erythema multiforme-like rashes.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Gout and Infectious Cellulitis

A 64-year-old man with known gout presented with a painful, swollen right third toe. He was initially treated in an outpatient setting for a gout flare with oral prednisone but had progressive worsening of pain, swelling, and redness of his lower extremity.

Examination revealed a nodular swelling of his right third toe, with an open ulceration draining whitish material that on microscopic examination showed numerous uric acid crystals (see images). Other examination showed red, tender swelling of his leg to the mid-shin.

An acute gout flare complicated by infectious cellulitis was diagnosed. The patient improved with a combination of oral steroids and antibiotics.

Take-home points:

• Gout flares may cause a cellulitic picture in absence of infection.
• In this case, infection and gout appeared to coexist, with infection probably resulting from tophus-related skin breakdown.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Infectious Endophthalmitis

A 73-year-old man presented with painful vision loss in his left eye that occurred over several days. He had no recent eye surgery. He also reported feeling feverish for several days before development of his eye symptoms. On examination, his left eye had yellowish crusting of the eyelid and opacification of the lens leading to difficulty in viewing the anterior chamber, although there was concern about a possible granulomatous process. There was also extensive edema and erythema of the conjunctiva.

Because of the possibility of granulomatous inflammation, there was some concern that rheumatic disease might be responsible for his eye findings. However, ocular and multiple blood cultures grew Streptococcus pneumoniae, and he was diagnosed with infectious endophthalmitis although the source of the infection was not found.

Take-home points:

• Infection of the eye may mimic rheumatologic disease.
• In most cases, bacterial endophthalmitis is secondary to local trauma or surgery. However, as in this case, hematogenously spread infection is possible.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Henoch-Schönlein Purpura

A 26-year-old woman presented with about 2 weeks of mildly painful and itchy purple lesions on her lower extremities that, on examination, were consistent with palpable purpura. An initial biopsy showed leukocytoclastic vasculitis; however, no immunofluorescence studies were performed.

A second biopsy again showed leukocytoclastic vasculitis, and on immunofluorescence, there was immunoglobulin A (IgA) deposition in the blood vessels.

On the basis of these skin findings, the patient was diagnosed with Henoch-Schönlein purpura (HSP) and improved with oral steroid therapy.

Take-home points:

• Numerous diseases, many of which are rheumatologic, can present with palpable purpura.
• HSP is more unusual in adult patients, although it can occur.
• IgA deposition on skin biopsy strongly suggests that HSP is the cause.
• If HSP is considered, immunofluorescence studies of the skin biopsy sample can help confirm the diagnosis.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Dermatomyositis Presenting as a Leg Rash

A 56-year-old woman presented with an enlarging leg rash. On review of systems, she also reported mild proximal weakness of her arms and legs. Her serum creatine phosphokinase level was elevated, and additional testing, including electromyography and muscle biopsy, confirmed a diagnosis of dermatomyositis.

The patient improved (including resolution of her leg rash) with oral steroids, methotrexate, and rituximab therapy.

Take-home points:

• Typically, rashes in dermatomyositis occur in sun-exposed areas and can include Gottron papules and heliotrope rashes.
• However, rashes may also occur elsewhere.
• In this case, the symptoms of proximal weakness led to the correct diagnosis.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Lymphocytic Interstitial Pneumonia in a Patient With Sjögren Syndrome

A 74-year-old woman with a longstanding diagnosis of primary Sjögren syndrome (SS) presented with cough and mild shortness of breath. Her diagnosis of SS was based on dry eyes and mouth, antinuclear antibody positivity, and SS-A and SS-B positivity. Chest imaging showed multiple thin-walled cysts consistent with lymphocytic interstitial pneumonia (LIP) (see images, where yellow arrows point out the cysts). She improved with treatment with a combination of oral steroids, azathioprine and rituximab. Of note, LIP can be a manifestation of mucosa-associated lymphoid tissue (MALT) lymphoma; however, in this case, there was no evidence of cancer.

Take-home points:

• LIP has a pattern on lung imaging consisting of cystic lesions.
• SS can be associated with LIP.
• When LIP is present, MALT lymphoma should be considered.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Finger Drop in Rheumatoid Arthritis

A 62-year-old man with rheumatoid arthritis (RA) presented with subacute onset of fourth- and fifth-finger weakness. On examination, there was evidence of radioulnar instability (piano-pedal deformity) and weakness in extension of the third, fourth, and fifth fingers.

Take-home points:

• Often referred to as "finger drop," this finding in patients with RA can stem from tenosynovitis and subsequent tendon rupture at the level of the wrist, slippage of extensor tendons into the lateral gutters at the level of the metacarpophalangeal joints (MCPs), or from injury to the posterior interosseous nerve (PIN) (a branch of the radial nerve that can be compressed at the level of the elbow from adjacent synovitis or other causes).
• Cases of suspected tendon rupture should be referred for hand surgery immediately; chronic tendon contractures are often not salvageable, and the patient is at risk for additional finger drop.
• Given the potential for PIN injury, be sure to examine the ipsilateral elbow closely for signs of synovitis.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

CPPD Disease Masquerading as Seronegative RA

A 60-year-old man with suspected long-standing seronegative RA presents to your clinic for the first time. His disease has primarily affected the bilateral wrists, MCPs, and knees. Acute flares of joint swelling respond moderately to prednisone, but he has had progressive disability and joint deformity despite treatment with methotrexate, adalimumab, and most recently infliximab.

Examination reveals bony enlargement and subluxation at the MCPs, with significant loss of range of motion at the wrists bilaterally. Radiographs were obtained. Joint aspiration followed by polarized microscopy revealed weakly positive, birefringent crystals consistent with calcium pyrophosphate, and calcium pyrophosphate deposition (CPPD) disease was diagnosed.

Take-home points:

• A medical provider who is faced with a patient in whom traditional therapy must consider several options: the patient has resistant disease, the patient is not compliant with medical therapy, or the initial diagnosis was incorrect.
• CPPD disease can present with acute exacerbations of inflammatory arthritis (pseudogout), but also with advanced degenerative arthritis due to calcium deposition within the cartilage followed by accelerated breakdown.
• Degenerative arthritis is common at the following peripheral joints: proximal interphalangeals, distal interphalangeals, first carpometacarpal, knees, hips, and first MTPs. In addition, the acromioclavicular joint and the cervical and lumbar spine can be involved. Involvement at other joints is atypical and warrants an evaluation for secondary causes, such as chondrocalcinosis.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Herpes Keratitis in an Immunosuppressed Patient

A 56-year-old man with granulomatosis with polyangiitis presents with left eye irritation and mild redness for 1 week. His disease has been characterized previously by sinus, pulmonary, and renal involvement. He was treated with rituximab 18 months earlier and has been in remission on maintenance azathioprine. On examination, he has mild conjunctival injection, but no obvious scleral inflammation. A slit-lamp examination was performed (see image). The rest of his physical examination was normal. On the basis of findings on slit-lamp examination, herpes simplex virus keratitis was presumptively diagnosed and treatment with oral acyclovir was started.

Take-home points:

• Many rheumatic illnesses can present with ocular manifestations, including scleritis, episcleritis, conjunctivitis, uveitis, retinal vasculitis, and orbital inflammatory disease, among others.
• In patients receiving immunosuppressive therapy, possible infectious mimics must be considered.
• Branching filaments on fluorescein staining are considered highly characteristic of herpes simplex virus infection, the most common corneal infection in the United States.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Neurologic Findings in Neuromyelitis Optica

A 60-year-old woman with long-standing lupus presents to the emergency department with subacute onset of bandlike tightness around her chest for 5 days, along with lower-extremity weakness. She has a negative ECG and troponin level. On examination, she has significant lower-extremity weakness and is unable to rise from the chair. She has decreased sensation to the lower extremities. Over the next 48 hours, she experiences complete bilateral loss of motor function of the lower extremities, and loss of sensation to the level of her breasts. Spinal MRI was obtained (see image), and treatment with intravenous steroids was started.

Additional laboratory testing was performed and was positive for neuromyelitis optica (NMO) IgG antibody. NMO spectrum disorder (NMOSD) was diagnosed. Rituximab induction therapy was started after pulse steroid delivery.

Take-home points:

• Complete, bilateral loss of sensory and motor function is indicative of a complete spinal cord lesion at a particular cord level.
• NMOSD is an autoimmune-mediated neurologic disease that can be associated with longitudinal cord lesions (three or more vertebral segments), optic neuritis, and characteristic brain lesions in the region of the third and fourth ventricles, and is often associated with NMO IgG antibody (a serum autoantibody that is directed against the aquaporin-4 receptor).
• NMOSD has been associated with concurrent systemic autoimmune disease (ie, systemic lupus and Sjögren syndrome)
• NMOSD can present with typical (optic neuritis, longitudinal myelitis) or atypical findings (area postrema syndrome, acute brainstem syndrome)

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD

Serotonin Syndrome in a Patient With Fibromyalgia

A 38-year-old female presents with worsening anxiety and restlessness for 2 months. She has noticed excessive sweating even at rest, as well as increased frequency of loose stools. She has had no sick contacts and denies travel. Her medical history includes irritable bowel syndrome, fibromyalgia, and anxiety.

Medications include amitriptyline 20 mg at night, venlafaxine 150 mg twice daily, and tramadol 100 mg three times daily as needed. On physical examination, the patient is slightly tachypneic with a borderline elevated temperature at 100.6° F. On neurologic examination, she has a slight resting tremor, and brisk (abnormal) deep tendon reflexes.

On the basis of these findings, there was high suspicion for serotonin syndrome due to medication interaction. Amitriptyline and tramadol were immediately stopped and the venlafaxine dosage was decreased by 50%, with close monitoring of symptoms.

Take-home points:

• Serotonin syndrome classically presents with changes in mental status as well as autonomic and neuromuscular hyperactivity. The syndrome represents a clinical spectrum spanning from milder to more severe presentations.
• Treatment consists of stopping the offending medications. In more severe presentations, immediate stoppage of all medications should be considered, and additional intervention, such as use of benzodiazepines, may be necessary.
• Selective serotonin reuptake inhibitors increase serotonin levels, but other medications can increase risk as well; these include amitriptyline, trazodone, and tramadol.
• Providers who manage patients with fibromyalgia should be aware of this syndrome, because offending agents are commonly used in combination for these patients.

Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD