7 multisystemic diseases every physician should watch for

By Naveed Saleh, MD, MS, for MDLinx
Published November 26, 2019

Key Takeaways

They say no man is an island. The same could be said of diseases. No disease totally affects only one part of the body. Everything in the body is connected somehow. For example, when you realize you have a disease—and if it’s serious enough—you may stress about it, which can be absolutely detrimental for your body. Stress can worsen pre-existing health conditions, and increase the risk of developing other mental, immune, endocrine, metabolic, and cardiovascular diseases.

Certain diseases seem to be entrenched in various organ systems—organ systems that are treated by different specialists, as well as primary care physicians. These diseases can be so varied in presentation and involve so many organs that they can’t be assigned to one main organ system, with examples including lupus, sarcoidosis, and polyarteritis nodosa.

With this in mind, here are seven multisystemic diseases that every physician should be aware of.

Systemic lupus erythematous

Nicknamed the “Great Imitator,” systemic lupus erythematous (SLE) is the prototypic autoimmune disease that can seemingly pop up everywhere in the body. People with SLE often present with a range of clinical symptoms that are nonspecific and may overlap with other medical illnesses, such as Sjögren syndrome and rheumatoid arthritis. Because of this, many patients have subclinical symptoms for years before accurate diagnosis, the prolongation of which can have a debilitating effect on the body.

SLE can not only affect the cardiovascular system via manifestation of valvular issues and carditis, but also affect the lungs, the brain and nervous system, the skin, the eyes, the legs and feet, as well as the gastrointestinal tract. Specific related complications can include pleural edema, headaches, seizures, vision problems, personality changes, patchy skin color, Raynaud phenomenon, uveitis, scleritis, conjunctivitis, lupus nephritis, abdominal pain, vomiting, and nausea.

To boot, this disease also elicits fatigue, chest pain, fever, mouth sores, weight loss, photophobia, and swollen lymph nodes, as well as malar rash in 50% of cases.


This disease involves the deposition of too much collagen in skin and other tissues. Because of this, scleroderma is often mischaracterized solely as a chronic skin disease. But, this autoimmune chronic connective tissue disorder affects far many more organs than just the skin.

There are two primary types of scleroderma: limited and diffused. Limited scleroderma—which means that only limited areas of the skin are thick—is the milder form of disease. This type of scleroderma largely affects patches of the skin, but can slowly progress to the lungs, esophagus, and blood vessels. Diffuse scleroderma, on the other hand, is much more severe, with more areas of the skin involved and thickened. This type of scleroderma progresses swiftly, causes swelling all over the skin, and hits the intestines, lungs, kidneys, and heart.

Lung involvement is a great concern with the disease, as both forms of scleroderma can cause shortness of breath due to interstitial lung disease (eg, pulmonary fibrosis), pulmonary hypertension, left heart disease, and muscle weakness and deconditioning. Other organ-specific complications of scleroderma often include severe gastroesophageal reflux disease, Barrett’s esophagus, scleroderma renal crisis, and digital infarction.

Polyarteritis nodosa

This vasculitis affects medium-sized vessels, including muscular arteries. Although it doesn’t usually interfere with the lungs, polyarteritis nodosa does affect the skin, joints, kidney, muscles, nerves, and intestines. Pathology involves vessel wall thickening—leading to vessel narrowing and ultimately arterial occlusion.

Systemic manifestations of the disease include hypertension, renal insufficiency, neuropathy, myopathy, mesenteric arteritis, mononeuropathy multiplex, and coronary ischemia.

Of note, generalized symptoms include weight loss, fever, and abdominal pain. Skin signs include palpable purpura, skin ulceration, and tender erythematous nodules reminiscent of erythema nodosum.


Granted, you probably know a lot about diabetes. But it’s always a good idea to reiterate the insidious effects of this chronic killer on a range of organ systems. Diabetes can affect the entire cardiovascular system, and cause heart diseases such as coronary artery disease, myocardial infarction, atherosclerosis, angina, and stroke. It can also affect the kidneys, causing nephropathy that may lead to end-stage renal disease and kidney transplant. People with diabetes are also at increased risk for developing skin and mouth infections, Alzheimer disease, hearing problems, and especially neuropathy—which can lead to glaucoma, cataracts, and blindness.

Aldose reductase could contribute to the pathogenesis of diabetes. This enzyme is the first in the intracellular polyol pathway, which plays a role in the conversion of glucose to sorbitol (glucose alcohol). High levels of blood sugar heighten the flux of sugar molecules via the polyol pathway, and lead to the hyperosmolar buildup of sorbitol in cells. Resulting osmotic stress may lead to microvascular complications, such as diabetic retinopathy.

Hyperglycemia can also lead to the formation of advanced glycosylated end products (AGEs). These glycoproteins can also lead to damage of the vasculature. Hyperglycemia results in oxidative stress via the buildup of free radicals and reactive oxygen species, which can cause cellular damage.

Behçet syndrome

Although first described by Hippocrates in the 5th century BC, this condition is named after Turkish dermatologist Hulusi Behçet, who documented the condition in 1937. Behçet syndrome is an autoimmune vasculitis, which usually affects people of Japanese, Mediterranean, and Middle Eastern descent.

Although this disease is characterized by recurrent mucocutaneous ulcers, including genital and aphthous ulcers, as well as uveitis and retinal vasculitis, other manifestations of the disease include: erythema nodosum and erythema multiforme; iritis, papilledema, chorioretinitis, and other ocular conditions; polyarthritis; thrombophlebitis; intracranial hypertension; cranial nerve palsy; and meningitis.

Symptoms of this condition include aphthous stomatitis, joint pain, morning stiffness, ulcers, and neurologic changes.


Sarcoidosis is a multisystemic autoimmune disease of unknown etiology that causes inflammation of the skin, lungs, and lymph nodes. The condition causes non-caseating, or non-necrotic, granulomas composed of inflamed tissue to develop in organs.

Sarcoidosis can affect any organ of the body, and symptoms are constitutional, including night sweats, cough, shortness of breath, and fatigue. Pulmonary symptoms include cough and dyspnea.

Patients with sarcoidosis often present with bilateral hilar lymphadenopathy and pulmonary infiltration, and frequently with ocular and skin lesions. However, other presentations that reflect the incredible breadth of organ involvement include: interstitial lung disease, pulmonary hypertension, cervical lymphadenopathy, cardiomyopathy, congestive heart failure, membranous glomerulonephritis, leukopenia, anemia, nephrolithiasis, kidney failure, peripheral neuropathy, and seizures.


Imagine a fire hydrant hosing down your arterial intima all day, every day… that’s essentially what happens with untreated hypertension. The effects of this high-pressure onslaught cause a variety of disruptions in all organs, not just the heart. Aside from the obvious heart attack and stroke, hypertension can cause hypertensive retinopathy, hypertensive chronic kidney disease, and metabolic syndrome. This oftentimes fatal condition can also affect the brain, causing aneurysm, cognitive impairment, and vascular dementia.

The next time you want to tickle your brain cells, visualize how these diseases impact various organ systems. Find the pathological throughlines!

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