Systemic Disease

Systemic disease or disorders can be defined as a disease that affects the whole body, rather than a single group of tissue or organ, as seen in localized conditions.

More than 45% of all illnesses are systemic diseases or have systemic implications. Several tissues and organs may be involved in this complex (systemic) disease process.

The condition is labeled complex because its manifestations affect the whole body in one or various ways.

However, not all disease starts as systemic; some health care providers often treat diseases that began as local and progressed to a systemic state.

For instance, in a pneumonia case, the condition might start in the lungs (either one or both) and spread throughout the body in a radically life-threatening condition known as sepsis.

In a pneumonia case, the pathogen responsible for pneumonia entered the bloodstream or lymphatic system and is transported to other body regions.

In this situation, what was once a localized infection has become a disseminated or systemic disease.

Another typical example of a localized to a systemic condition mostly treated by an oncologist (an internist or specialist who possesses additional training to specialize in cancer patients) is cancer metastasizing from a region into other organs, blood, or the bones.

Systemic diseases act as risk indicators for oral, respiratory tract, ocular, or general health problems.

Systemic diseases like diabetes can serve as a risk factor, predisposing a patient to significant oral problems (oral issues as a case study) such as oral ulceration, stomatitis, infection, and poor wound healing.

Indeed a poorly controlled diabetic is more likely to have periodontitis. In conditions of age-related macular degeneration (AMD), several systemic diseases have been closely linked to AMD’s risk.

It has been reported in some epidemiological researches that hypertension, some cardiovascular disease, and diabetes mellitus (all systemic disorders) to be associated with increased AMD prevalence.

However, the relation of other systemic diseases with AMD remains hidden due to inconsistent data.

Revealing the link between AMD and systemic diseases would contribute to more understanding of the pathophysiology of AMD, allowing for screening of patients at risk, and ultimately may help prevent AMD.


Causes of systemic disease entail as much as the list of the examples of this disease classification.

But some of the common etiological links to systemic diseases include:

  • Allergic reactions
  • Autoimmune inflammatory origin
  • Genetic mutation etiology
  • Inherited diseases and blood disorders
  • Imbalances in levels of blood cells
  • Metabolic disorders
  • Imbalance blood sugar level
  • Inflammatory origins
  • Connective tissue disorders
  • Irregular blood and pulmonary pressure
  • Viral infection
  • Bactria infection
  • Fungi infections
  • Nematodes and protozoa infections
  • Hormonal insufficiency or Endocrine imbalance
  • Systemic vasculitis
  • Blood vessels hardening such as atherosclerosis
  • Trauma to the Brain
  • Central Nervous System disorder or irregularities and so on.

As long as a condition affects several parts of the body, it is regarded as a systemic disease. As earlier stated, some of these systemic diseases might begin as localized and use the blood, lymphatic or nervous system as a means of transport to other locations.

The blood, lymph, and nerves can be affected during this transporting process.

Types of Systemic Disease

The list of types and even common kinds of systemic diseases are endless. However, here we will be categorizing and summarizing as much as we can base on the etiologies of systemic disease, to cover as many examples as possible:

Skin and Mucous Membrane Systemic disease

These systemic diseases are mostly immunologic disorders of the skin and mucous membranes, they include:

  • Acne rosacea
  • Albinism
  • Atopic dermatitis
  • Behḉet’s disease
  • Cicatricial pemphigoid
  • Ehlers-Danlos syndrome
  • Epidermolysis bullosa
  • Erythema multiforme
  • Erythema multiforme major (Stevens-Johnson syndrome)
  • Goltz-Gorlin syndrome
  • Ichthyosis
  • Incontinentia Pigmenti
  • Nevus of Ota
  • Paget’s Disease
  • Pemphigus
  • Pseudoxanthoma elasticum
  • Psoriasis
  • Vitiligo
  • Vogt-Koyanagi-Harada syndrome
  • Xeroderma Pigmentosum


This is a group of systemic diseases primarily affecting the central nervous system and peripheral nervous system, skin, eye, and viscera.

Many of these systemic diseases possess a well-defined pattern of inheritance due to a single gene mutation.

  • Louis-Bar Syndrome (Ataxia telangiectasia)
  • Neurofibromatosis (von Recklinghausen’s disease)
  • Racemose hemangiomatosis (Wyburn-Mason syndrome)
  • Sturge-Weber Syndrome (Encephalotrigeminal angiomatosis)
  • Tuberous sclerosis (Bourneville’s syndrome)
  • Von Hippel-Lindau disease (retinocerebellar capillary hemangiomatosis)

Collagen systemic disease

This is a term used to describe systemic autoimmune diseases, particularly those thought to be associated with collagen defects (a connective tissue component).

They include:

  • Ankylosiing spondylitis
  • Dermatomyositis
  • Ehlers-Danlos Syndrome
  • Periarteritis nodosa
  • Reactive arthritis
  • Relapsing polychondritis
  • Rheumatoid arthritis
  • Sarcoidosis
  • Scleroderma
  • Systemic lupus Erythematosus
  • Temporal arteritis
  • Granulomatosis with polyangiitis

Systemic Allergic disease

Systemic disease as a result of allergic reactions:

Systemic disease due to viral infection:

Systemic disease as a result of bacterial infections:

Systemic diseases caused by a fungi infection:

  • Actinomyces
  • Candida albicans
  • Coccidioidomycosis
  • Cryptococcus
  • Histoplasmosis
  • Metastatic fungal endophthalmitis
  • Streptothrix

Systemic diseases due to protozoa infection:

  • Chlamydia (Inclusion conjunctivitis)
  • Chlamydia (Lymphogranuloma venereum)
  • Malaria
  • Toxoplasmosis

Systemic diseases due to cestode and nematode infections:

  • Cysticercosis
  • Echinococcosis
  • Loiasis
  • Onchocerciasis
  • Toxocariasis
  • Trichinosis

Hematologic systemic disease:

Systemic disease caused by chromosomal and genetic syndromes:

  • Ciliopathic genetic syndrome
  • Cri-du chat syndrome
  • Deletion of Chromosome 18
  • Down syndrome (Trisomy 21)
  • Edwards’ syndrome (E-syndrome, Trisomy 18)
  • Monosomy-G syndrome
  • Patau’s Syndrome (D-syndrome, Trisomy 13)
  • Ring-D chromosome
  • Schmid-Fraccaro syndrome
  • Turner’s syndrome

Endocrine System Diseases

  • Cushing’s disease
  • Addison disease
  • Diabetes mellitus
  • Hyperparathyroidism
  • Hypoparathyroidism
  • Hyperthyroidism
  • Hypothyroidism

Cardiovascular Systemic Diseases:

  • Aortic arch syndrome
  • Arterial spasm (TIA)
  • Arteriosclerosis
  • Cardiac myxoma
  • Carotid artery disease
  • Central retinal artery occlusion
  • Cranial arteritis
  • Emboli and thrombi
  • Endocarditis
  • Hereditary telangiectasia (Rendu-Osler-Weber syndrome)
  • Hypertension
  • Myxoma
  • Pre-eclampsia
  • Thromboangiitis obliterans
  • Thrombosis

Systemic diseases due to Gastrointestinal and nutritional disorders:

  • Alcoholism
  • Crohn’s disease
  • Hypervitaminosis A, B, and D
  • Liver disease
  • Malnutrition
  • Pancreatic disease
  • Peptic ulcer disease
  • Regional enteritis
  • Vitamin A, B, C deficiency
  • Whipple’s disease

Systemic diseases resulting from metabolic disorders:

  • Alkaptonuria
  • Amyloidosis
  • Chediak-Higashi syndrome
  • Cystinosis
  • Fabry’s disease
  • Gaucher’s disease
  • Gout
  • Galactosemia
  • Hemochromatosis
  • Histiocytosis
  • Homocystinuria
  • Lipidoses
  • Marfan’s syndrome
  • Mucopolysaccharidosis
  • Niemann-Pick disease
  • Osteogenesis imperfecta
  • Weill-Marchesani syndrome
  • Wilson’s disease

Systemic diseases that are caused by Musculoskeletal disorders:

  • Albright’s disease (fibrous dysplasia of bone)
  • Apert syndrome
  • Conradi’s syndrome
  • Craniofacial syndrome
  • Facial deformity syndromes
  • Muscular dystrophy disorder
  • Myasthenia gravis

Systemic diseases that are caused by Pulmonary dysfunction:

  • Bronchiectasis
  • Bronchogenic carcinoma
  • Cystic fibrosis of the pancreas
  • Emphysema
  • Pneumonia
  • Tuberculosis

Systemic diseases due to Renal disorders:


Common cutaneous (skin) symptoms that systemic disease can present include:

  • Blisters and granuloma annulare- Diabetes mellitus
  • Dark red nodules formation- Mastocytosis
  • Dry and Scaly skin- Hypopituitarism, Hypothyroidism
  • Erythema nodosum- Sarcoidosis
  • Generalized itching
  • Hyperkeratosis- carcinoid syndrome
  • Jaundice- Sickle cell anemia
  • Palm Erythema – Liver disease and Rheumatoid arthritis
  • Photosensitivity- Myelodysplastic syndrome
  • Purpura
  • Seborrhoeic dermatitis- HIV and AIDS
  • Spider naevi
  • Xanthelasmata

Some Oral manifestations include in systemic diseases are signs indicated in the buccal (mouth and cheek) cavity. Some systemic diseases with oral manifestations include:

  • Change in mucosal pigmentation
  • Dental erosion
  • Mucosal pallor
  • Oral lesions
  • Oral ulcerations
  • Periodontal inflammation and bleeding

Ocular manifestations are one of the precise indicators of systemic disease. Almost any part of an eye can give relevant clues to the diagnosis of systemic disease.

Common ocular manifestations (manifestation of the anterior and posterior regions of the eyes) of systemic diseases include:

  • Cataracts- Down’s syndrome, Cushing’s syndrome, Atopic dermatitis, Congenital rubella, Refsum’s disease, Hypoparathyroidism, Lowe’s syndrome, and muscular dystrophy.
  • Conjunctivitis and uveitis- Reactive arthritis, Sarcoidosis, VKH syndrome, Psoriatic arthritis, Steven-Johnson Syndrome, Tuberculosis, and toxoplasmosis.
  • Corneal arcus- hyperlipidemia
  • Corneal ulceration- Hyperthyroidism
  • Dry eyes- rheumatoid arthritis
  • Glaucoma- Diabetes and Sturge-Weber syndrome
  • Hard exudates (fatty deposits)- diabetes
  • Ischemic swelling- hypertension
  • Kaposi’s sarcoma- HIV/AIDS
  • Keratitis- Herpes, fungal and Bacterial keratitis,
  • Lack of Pigmentation and poor vision-Albinism, Leukemia
  • Optic atrophy- Acromegaly
  • Proptosis- Grave’s disease
  • Retinal vasculitis- Systemic lupus erythematosus, Behḉet’s disease, HIV retinopathy, choroiditis, B-cell intraocular lymphoma.
  • Small vessel hemorrhage- Anemia, Hypertension, Giant cell arteritis
  • Vascula occlusions- Sickle cell disease and thalassaemias.

The Skin: Primary Diagnosis tool for Systemic Diseases

Due to the well-known fact that systemic diseases affect the whole body, the body’s changes are usually generalized pr nonspecific, making it a stumbling-block in identifying the condition based on diagnostic tests alone, such as imaging features.

Diagnosis of systemic diseases mostly involving analyzing physical manifestations of the skin, eyes, and viscera tissues.

For instance, the skin is a definite functioning system that is linked and communicates with changes in the internal environment.

Skin sign of systemic diseases is most common diagnosis trend to identifying first symptoms of internal diseases.

Also, these changes may be sole expressions of contrarily asymptomatic systemic disorders. Several signs and disorders of the skin can be valuable markers of systemic disease.

However, specialized modern diagnostic tests such as blood tests, Imaging Scans, X-rays, biopsy lab tests, vasculitis, ocular, or oral manifestations are available.

The skin still stands as the first and only organ of the body that is entirely and immediately accessible to direct clinical examination.

The evaluation of the abnormal features of skin lesions observed in many internal diseases is always helpful to doctors, internists, and dermatologists in diagnosing systemic disease.

Prevention and Treatment

Unfortunately, not all systemic diseases have a cure. The key to prevention and generalized treatment of systemic disease is maintaining a quality life while living with or without systemic disease.

To decrease disease progression, reduce inflammation, relieve pain, and improve system functions, doctors may suggest any of the following options:

  • Surgery
  • Medications
  • Lifestyle changes through proper and regular physical therapy and exercises.

Evaluation for Systemic Disease

The prevalence of various systemic diseases was investigated using a self-reported questionnaire regarding doctors’ diagnoses in health interview surveys.

Participants were questioned twice about their systemic disease status. The first question is for the existence of the disease, and the second for the doctor’s confirmation of the diagnosis.

For example, the first question for diabetes was, “have you ever had diabetes?” The second question was, “was the diagnosis of diabetes confirmed by your doctor?” Only those who answered in the affirmative to both questions were considered to have the systemic disease.

This same investigative procedure (use of questionnaire) was employed for other common systemic diseases, but with few inclusions of multiple diagnostic criteria and vast information were correlated, revealing response rate, population distribution, extraction rate.

Continuous variables were also expressed as mean ± SE or mean with 95% confidence intervals (CI). These continuous variables were examined using odds ratios (Ors) with 95% confidence intervals (CI).