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Diagnosis Deconstructed

Diagnosis Deconstructed: A Mystery Beyond Palpation

Morchi, Ravi MD

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doi: 10.1097/01.EEM.0000449778.75481.87

    It all started with a fall in the shower 10 days before. “Did you hit your legs against anything when you fell? Did your toes bend or crack?”


    So that doesn't explain what I'm seeing. The physical doesn't match up. An incorrect story? The true cellular order of events does not always follow the causal relationship our patients perceive.

    Leaving behind the history. I cannot deny what I see. Something has been going on, but mechanical trauma is not the cause.She is a middle-aged obese woman in no distress. Afebrile, pulse 98, BP 117/67. Other than her weight, the physical exam from scalp to knees is normal. Below that it is not.

    My attention is drawn to a half-dozen bilateral scattered ulcerations appearing punched out of her pretibial skin, each one less than 0.5 cm. Most are dry, but some have serous drainage. The edges are not raised. Edema and patchy erythema populate the intervening dermis.

    These are not the classic neuropathic ulcers occurring on the plantar surface when bone pounds against floor, and craters with a thick hypertrophic rim emerge over metatarsal prominences.They are not lakes of shallow denuded dermis over malleoli amid hyperpigmented skin from elevated venous pressure and extravasated and phagocytosed RBC products. They are not stasis ulcers.

    Knees and ankles have full passive range of motion. No joint effusion.

    Erythema descends from her pretibial skin over the dorsum of each foot, adopting splashes of purple. An ecchymotic hue to “cellulitis” may indicate blood products extravasated from damaged capillaries. Capillary damage in her case is neither traumatic nor infectious. With bilateral and relatively symmetric findings, her necrosis of capillaries, like her pretibial ulcerations, is ischemic.

    Toes. Ecchymoses deepens distally down to digits. The tips of the most purple toes have spots of dry gangrene. Looking closely at her skin, I peel it off and then excise all muscle, and skeletonize the arterial system. Follow it from toes up to trifurcation and further to aortoiliac bifurcation. Is this atheromatous disease with thrombosis atop ruptured plaques littered along the way? I look at her face. She seems too young.

    Are thromboemboli lodged at the aortoiliac bifurcation or the lower leg trifurcation on both sides, extending down distal tributaries? I briefly remove her thoracic cage, retract the left lung medially, and follow the aorta up through the posterior mediastinum to the aortic valve, into the ventricular lumen, mitral valve, and atrial appendage. Glancing from her chest back at her hands:no findings. Perfusion is normal; no lesions. I have her turn on her side, and scanning over the perineum and buttock, I note absence of ischemic ulcerations in the internal iliac distribution. This is not cardioembolic. Corroborating evidence in negative blood cultures and echocardiograms would be available days later, but now I replace the thoracic cage, and follow the blood below the diaphragm.

    Pulses. Femoral, DP, and PT are equal bilaterally. The circumference of her thigh and lower leg preclude BP cuff placement to quantify ABIs. Regardless, the cumulative evidence tells me that the main arterial tree is intact and that neither thrombosis in situ nor thromboemboli are likely. With open macrovascular highways, the problem has to be the off-ramps.

    Microvasculature. A small vessel issue obstructing exit lanes distal to the major artery palpation sites. Microvascular insufficiency without an atheroembolic or endocardial source. A CT angiogram later confirms no filling defects.When it comes to arterioles, our eyes are not privy to end organs other than the skin and retina. But adjuncts and deconstruction can help us see viscera.

    Creatinine of 2.1 and UA with 2+ protein, a handful of RBCs, and granular casts. Glomerulonephritis because of the same arteriolar insufficiency.

    Progressive hypertension. Blood pressure trended upwards to 245/139. Afferent renal arteriolar obstruction leading to a selfish distal juxtaglomerular reaction, increase in renin with activation of the angiotensin and aldosterone cascade. The rest of the body erupts in a hypertensive crisis from systemic vasoconstriction and volume retention while starved JGAs pour out renin in hopes of sustaining their own perfusion.

    Progressive somnolence. Mentation declined as her BP rose.Cerebral dysfunction from vascular pressure well outside auto-regulatory capabilities. Compounding this was the same dermal and renal microvasculitis now setting into multiple cerebral off-ramps. There is a traffic jam, a major Los Angeles traffic jam, in her brain. Head CT showed hypertensive ischemic changes. No blood.IV blood pressure control was initiated and heparin started to dissuade fibrin cross-linking bumper-to-bumper vehicles.

    Diagnosis? More powerful than reciting a list of memorized eponyms and acronyms, our approach to microvascular disease as general physicians should be seated in mechanism.

    Arteriolosclerosis. The standard thickening of arteriolar walls that eventually occludes lumens. It occurs in the setting of longstanding hypertension and diabetes. It is not an “itis” but rather a gradual, progressive vasculopathy. Many of our ED patients have this. She does not.

    Vasculitis. This is a neutrophilic and sometimes granulomatous infiltration in vascular walls. Arrays of names are affixed to large and small vessel versions. In our case, it would be arterioles and maybe venules. Surgery will not help. It occurs distal to all potential bypass sites.

    Antigen-antibody mediated processes. Instead of the wall being the primary problem, inflammation starts with antibodies directed against the endothelial lining or against a circulating antigen that deposits in a symmetric fashion in the lower extremities. A secondary inflammatory cascade ensues within the lumen. Hypersensitivity drug reactions, HSP, and cryoglobulins are a few entities in this category.

    In our patient, thrombosis followed inflammation and dermal erythema turned purple and later black. Whatever its mechanism, it was moving faster than anything I had ever seen.

    Three options. Glucocorticoids or another more potent immunomodulator to discourage the inflammatory reaction, IVIG to coat a purported antigen or to saturate Fc receptors on immune cells limiting their ability to react, and plasmapheresis to remove the antibody and circulating antigen.

    She received all three therapies multiple times after a rheumatology consult. A dermatology biopsy showed nothing more revealing than mind's eye: vascular occlusion and necrosis of surrounding tissue. Infectious, metabolic, and rheumatologic serum assays investigating primary vasculitides, antibody-directed processes, and TTP were negative. She received broad-spectrum antibiotics in case the origin of endothelial injury proved infectious, but no organism ever turned up.

    As her platelets were consumed, daily inpatient summaries regurgitated the term catastrophic antiphospholipid antibody syndrome (CAPS), the name for the antibody-antigen process they believed was rapidly occluding small vessels. But her anticardiolipin and lupus anticoagulant studies also returned negative.

    She ended up in the ICU for progressive cerebral dysfunction and greedy glomerulii. Soon her destructive microvascular occlusion took down multiple organs resulting in DIC, hepatic necrosis, and loss of vascular tone. Intubated and on pressors, she coded and was found to be missing hemoglobinwhen resuscitated. Inflamed, fragile vessels in her retroperitoneum brought devitalizing capabilities to our heparin drip and her consumptive coagulopathy. More than three liters of hemoretroperitoneum was removed and the area packedduring an emergent OR visit. She never saw heparin again, and she never woke up. She was made DNR/DNI and died.

    I do not know whose eponym or syndrome will eventually be appended to this “itis” or antibody. If it is not CAPS, consider that a term for it may not yet exist. The body is thousands of years in the making, and our medical knowledge is not. Many undiagnosed entities distal to the palpable point of arteries remain to be named.

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