Livido reticularis

A healthy person's skin has a more or less uniform color in a particular area. There is no pattern or inclusions of a different color on it, with the exception of moles and traces of insect bites. But in some people, under the influence of cold, an unusual bluish or burgundy pattern appears on the body in the form of an indistinct mesh, outwardly resembling marble. This phenomenon is called in medicine mesh livedo or Livedo reticularis.

The reader may have heard other names for this condition, which is a normal physiological reaction of peripheral vessels to cold. Names such as marbled skin or livedo reticularis all refer to the same pathology, although it would be a stretch to call this condition a pathology.

Causes of reticulated livedo

It is simply impossible to name a specific reason for the appearance of a marble pattern on the skin. This is due to the fact that the mesh livedo has two mutually exclusive forms:

• Idiopathic livedo. This is an unstable physiological reaction of the body that occurs under the influence of cold air and passes when the body is exposed to heat. No irreversible morphological changes in the structure of the vascular walls occur.

The pattern appears on exposed parts of the body that are not protected from the cold by clothing. This form of livedo can be seen on the body of young women.

The causes of idiopathic livedo still remain a mystery to doctors, although it is well known that the marble pattern appears as a result of vascular spasm. Why this pattern appears in some people and not in others remains unclear. But since this phenomenon, in the absence of any vascular pathologies, is not considered a disease and does not require treatment, its study is not given much importance.

• Symptomatic livedo. The name of the condition itself indicates that the mesh pattern on the skin is one of the symptoms of some pathologies in which the blood flow to the skin is disrupted.

Symptomatic livedo reticularis can be observed in the following pathologies:

• High blood viscosity, heart failure, paralysis, Sneddon syndrome, cholesterol embolism syndrome, thrombocytosis and some other diseases in which there is a violation of blood flow through the vessels as a result of obstruction.
• Atherosclerosis of blood vessels, vasculitis: polyarteritis nodosa, lupus erythematosus, cryoglobulin vasculitis (cryoglobulinemia), rheumatoid arthritis, AFL syndrome, lymphoma, dermatomyositis, syphilis, tuberculosis, pancreatitis and other pathologies in which changes occur in the vascular wall.

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Risk factors

Risk factors for the development of livedo reticularis include:

• Taking certain medications. For example, quinine, amantadine, quinidine, norepinephrine.
• Hypothyroidism in the mother, which can be transmitted to the fetus. After birth, livedo reticularis, along with symptoms such as cold hands and feet, apathy to the environment, drowsiness, etc., can be seen in a baby with low levels of thyroid hormones.
• Autoimmune thyroiditis, which, like vasculitis, may develop livedo reticularis as a consequence of hypothyroidism, especially if the patient has light, thin skin.

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Pathogenesis

The word "livedo" itself, translated from Latin, means a bruise. A bruise is nothing more than a limited accumulation of blood in the subcutaneous layer or simply a hemorrhage. Bruises, or hematomas, are usually formed as a result of tissue damage, during which capillaries rupture. Blood, flowing out of the vessels, accumulates in the subcutaneous tissue and is externally visible as a blue area of the body.

With livedo, extensive subcutaneous hemorrhage is not observed. Under the influence of certain irritants (most often cold), a spasm of the vessels occurs, characterized by disturbances in capillary blood flow, resulting in stagnation of blood in the veins, and the vessels become visible through the layers of skin.

Livedo is a vascular neurosis of the spastic-atonic form. The vascular pattern resembles either the branching of a tree (dendritic livedo) or a mesh or marble surface (reticular or reticular livedo). In the reticular variety of livedo, blood stagnation causes thickening of the endothelium in the venous knee of the capillaries, and this part of the vessel begins to show through the skin. This is what determines the type of pattern that we see on the surface of the body.

According to statistics, reticular livedo is more common than dendritic and other types of livedo (with a speckled or bizarre pattern). This type of vascular reaction is more typical for girls aged 20-23, although sometimes a similar pattern can be found in older people (more often women) (up to 50 years) with delicate, light-colored skin.

The specific vascular pattern appears predominantly in the area of the shins and thighs, although sometimes it can also be seen on the forearms, sides of the body, hands and buttocks.

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Symptoms of reticulated livedo

The main symptom of livedo reticularis is the appearance of a marble pattern with a bluish tint on the body and limbs, which becomes more pronounced and bright under the influence of cold or sudden temperature changes, and disappears when pressed. Idiopathic livedo practically does not appear in the summer. It "prefers" colder periods.

The color of the pattern can vary from reddish-violet to burgundy and even blue. The "mesh" has no clear boundaries. The "mesh" cells can be round or oval. Their diameter can reach 20 mm. The skin inside the so-called cells can be of normal color or slightly paler than the rest.

Idiopathic livedo reticularis is characterized by a certain symmetry. The pattern appears not on one limb, but on both at once. It can be located on the buttocks or on the sides of the body. By the way, separate asymmetrical spots can sometimes be observed on the arms and legs. Symptomatic pathology with a marble pattern is not characterized by symmetry.

People with idiopathic livedo may feel cold in a fairly warm room, and their perception of temperature is impaired. The hands and feet of such patients are usually cold to the touch due to impaired blood circulation. When the vascular network appears, slight pain and tingling may be felt. Sometimes, sensitivity disorders and numbness of the skin are noted.

Symptomatic livedo is always the first sign of some pathology, in which there is an obstructive disorder of blood flow or morphological changes in the vessels, as a result of which the blood flow is again disrupted. In this case, other symptoms characteristic of the existing pathology are added to the drawing on the body.

For example, if a person has increased blood viscosity, they suffer from headaches, tinnitus, chronic fatigue, drowsiness and depression. Such patients have an increased risk of nosebleeds, often have high blood pressure, and have certain vision problems. Patients note impaired body sensitivity with tingling and "goosebumps". Along with reticular livedo, they may have noticeable venous nodules.

Vasculitis is characterized by the appearance of a marble pattern on the skin, which is called livedo vasculitis (otherwise, livedo angiitis). The pattern is present constantly and is characteristic of many types of vasculitis. It resembles a looped network, which becomes brighter under the influence of cold, but does not disappear from heat, as in idiopathic livedo. The disease progresses, and livedo becomes more pronounced, foci of hemorrhage and necrosis appear on the mesh with the subsequent formation of small ulcers.

In severe cases, painful nodules form in the vascular network, prone to necrosis and the formation of deep ulcers in their place, which heal over a long period. The ulcers heal with the formation of light scars, surrounded by skin that is darker than normal.

Patients complain of constant chilliness. They note unpleasant nagging pains in the extremities, while in the area of ulcers and nodular compactions the pain has a pronounced pulsating character.

The occurrence of livedo angiitis is noted predominantly in females.

In Seddon syndrome, a type of antiphospholipid syndrome (APL), along with the marbled pattern on the skin, there are symptoms indicating high blood pressure and cerebral vascular thrombosis. APL itself is characterized by venous and arterial thrombosis, lesions of the central nervous system and heart (coronary artery thrombosis).

In cholesterol embolism, the appearance of a vascular pattern may remain the only symptom for some time. And the diagnosis is made on the basis of a skin biopsy.

Symptoms of atherosclerosis of blood vessels may vary depending on which area of the blood vessels are affected.

If livedo reticularis is accompanied by increased sweating, cyanosis of the skin, chills, and keratinization disorders, a person should consult a doctor, since such symptoms may indicate various pathologies associated with circulatory disorders.

Physiological livedo in infants

Newborn babies have especially delicate and thin skin, which normally has an even color. If parents notice a bluish mesh-like pattern on the baby's body, they are very frightened, although in a baby, as in an adult, the appearance of mesh livedo is not always associated with health pathologies.

In a child under 6 months, the periodic appearance and disappearance of a strange pattern on the skin can be associated with insufficient formation of the immune system, the thermoregulation system, as well as the location of blood vessels near the thin skin. Therefore, when exposed to cold air and due to temperature changes, the body reacts by appearing a marble pattern. It disappears as soon as the body adapts to the ambient temperature, but this process is slower in infants than in adults.

Marbled pattern on the skin of a baby can occur as a result of prematurity or birth hypoxia. Its appearance is also associated with overfeeding the child, which provokes an increase in blood volume and stretching of blood vessels. In thin children with low weight, the appearance of reticular livedo is considered a normal variant.

But livedo reticularis in an infant may also be a manifestation of such rare congenital pathologies as telangiectatic cutis marbled, which is also called generalized phlebectasia, and the mysterious cutis marbled syndrome.

Constant or periodically appearing livedo stipple can be observed in children with heart defects, congenital glaucoma, genetic anomalies, vegetative-vascular disorders. Marbled pattern can also appear with anemia, rickets, non-inflammatory diseases of the brain.

Sometimes with age this symptom disappears and no longer reminds of itself. If this happens at the age of up to 5 months, then there is nothing to worry about. If the pattern on the skin remains for a longer time, it is best to examine the baby to identify the pathology that caused such a symptom at an early stage.

Complications and consequences

Idiopathic livedo reticularis does not pose a danger to human life and health. In this way, the body and, in particular, the vascular system react to cold. When warmed up, the marble pattern disappears without a trace. And since no structural changes occur in the vessels during this time, this condition does not cause harm to health.

But this is the case if idiopathic livedo is not accompanied by livedo vasculitis, which is characterized by the formation of nodules and ulcers. And any damage to the skin is considered a breeding ground for bacterial infection. Especially when it comes to deep and difficult-to-heal wounds.

Sometimes, in addition to ulcers in the area where livedo reticularis appears, tissue edema is also observed, which is considered a complication of livedo reticularis.

The consequences of livedo retinalis depend on the pathology that caused the appearance of the corresponding pattern on the body. The most dangerous is the formation (and especially the detachment of a thrombus). But other pathologies, in which there is a violation of blood circulation, are not very pleasant, since they cause oxygen starvation of various tissues and organs, as a result of which they can no longer perform their functions normally.

If we are talking about disturbances of coronary and cerebral blood flow, then here we see a situation that is dangerous not only for the health, but also for the life of the patient.

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Diagnostics of reticulated livedo

If a person notices the appearance of a strange pattern on the skin, which becomes brighter when exposed to cold, and fades when warmed up until it completely disappears, it is not so easy to determine by eye whether this condition is associated with a normal physiological reaction of the body or is a sign of serious systemic diseases.

If the appearance of the pattern is associated only with the effect of low temperatures, at which vascular spasm occurs, then, most likely, there is no need to worry. But if the pattern does not disappear when warmed up, but only slightly fades, this is already a reason to contact a medical institution for a doctor's consultation and examination of the body, and blood vessels in particular. After all, the pattern that we see is nothing more than a vascular network, which in a normal state should not be visible.

During the appointment, the specialist examines the patient, palpates the affected area, listens to and taps the chest area, measures blood pressure and pulse, and collects anamnesis. If the patient is a small child, it is necessary to find out what diseases the mother had before and during pregnancy, how the pregnancy proceeded, how and at what stage the birth took place, clarify when the pattern appeared on the baby's body and whether there are any other alarming symptoms, especially those that we have already mentioned above.

The patient is prescribed tests. Usually, this is a general and biochemical blood test. The blood gas composition is determined to clarify its oxygen saturation. A urine test may also be prescribed to prescribe safe treatment and determine kidney function.

The doctor may also order a respiratory function test. The study of external respiratory functions includes spirometry, pneumotachography and spirography, which are used to assess the functionality of the lungs, and therefore the volume of oxygen entering the blood.

Instrumental diagnostic methods that can be prescribed for livedo reticularis include:

• angiography (assessment of blood supply to organs) of vessels,
• phonoangiography (assessment of vascular noises in case of blood flow disorders) of vessels,
• volumetric sphygmography (determines vascular wall vibrations to assess main blood flow),
• rheovasography (assessment of central and peripheral
• skin electrometry and thermography (assessment of the state of peripheral circulation based on changes in skin temperature),
• Duplex scanning with ultrasound Dopplerography (assessment of the general condition of the vessels and blood flow in them),
• Ultrasound of blood vessels (determines areas of vascular stenosis),
• Radioisotope examination (studies the blood filling of peripheral vessels),
• Nuclear magnetic resonance imaging with contrast (assessment of the condition of the vascular wall, minute blood flow, length of stenotic vessels, etc.).
• endoscopic examination of the tracheobronchial tree through which air enters the lungs (fibrobronchoscopy),
• lymphography (assessment of lymph flow, used for edema syndrome),
• electro- and echocardiography.

There are other methods for assessing the condition of the main and peripheral vessels, but the above-mentioned research methods are the most popular in domestic medical institutions.

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Differential diagnosis

Differential diagnostics are performed when edemas appear (the nature of the edemas and what causes them) and symptoms characteristic of various pathologies. Livedo reticularis also needs to be differentiated from reticular skin pathologies such as infrared and infectious erythema, poikiloderma, reticular varicose veins, etc.

But first of all, it is important to distinguish between the idiopathic form of livedo and the symptomatic form associated with certain diseases that pose a threat to the health and life of the patient.

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Treatment of reticulated livedo

If livedo reticularis is not a permanent symptom and is diagnosed as idiopathic, then it does not require any treatment. Such a reaction may be present for a limited time and disappear with age, or it may become chronic. However, it does not pose a danger to humans, which means there is no need to treat it.

True, sometimes, if the appearance of the vascular network causes severe discomfort, the doctor may prescribe small doses of "Acetylsalicylic acid" and "Pentoxicillin" (400 mg three times a day). Such treatment does not require hospitalization. It is prescribed by a therapist or dermatologist.

Treatment of symptomatic livedo is carried out taking into account the pathology that caused the appearance of the marble pattern on the body.

In most cases, doctors prescribe:

• Vasodilators, primarily peripheral vasodilators, which ensure normalization of blood flow by relaxing the vascular walls (Pentoxifylline, Vazonit, Pentomer, etc.).
• Blood thinning drugs (Aspirin, Heparin, Warfarin, etc.).
• Calcium preparations.
• Vitamins or vitamin-mineral complexes containing calcium, vitamins C, E, P, nicotinic acid, which improve the condition of blood vessels, reducing their fragility and permeability.
• If your blood pressure is high, medications used to combat hypertension may be prescribed.
• In case of vasculitis, therapy with glucocorticosteroids (Prednisolone) and immunosuppressants (Azathioprine, Cyclophosphamide) is prescribed; in some cases, cytostatics are indicated, as in case of lymphoma.
• If there is an inflammatory reaction, then non-steroidal anti-inflammatory drugs (most often "Indomethacin") and antimicrobial agents are prescribed to relieve inflammation and reduce pain when ulcers and areas of tissue necrosis appear.
• In some cases, if drug therapy does not bring tangible results, chemotherapy and blood purification procedures (hemosorption and plasmapheresis) may be prescribed.

In livedo reticularis, physiotherapy gives good results: hirudotherapy, massage, ultraviolet irradiation of the affected area with suberythemal doses (from 1/8 to 7/8 of the usual biological dose), heat exposure (mainly warm baths). Such treatment can be prescribed for both symptomatic and idiopathic livedo.

Surgical treatment for livedo reticularis is not performed unless the pathology is associated with severe vascular diseases that do not respond to drug treatment. Otherwise, an operation corresponding to the underlying pathology may be prescribed.

Medicines for livedo reticularis

Livedo reticularis, like other circulatory disorders, requires first of all the prescription of drugs that relieve vascular spasm and relax vascular muscles, which results in normalization of blood flow and oxygen supply to various organs. Such drugs are called vasodilators.

In the case of livedo reticularis, the problem most often lies in the peripheral vessels, which means that the doctor, in the absence of other disorders, will prescribe medications from the category of peripheral vasodilators.

The most popular and inexpensive drug from this group is considered to be "Pentoxifylline". It is prescribed for various disorders of peripheral circulation, including reticular livedo of various etiologies.

Method of administration and dosage. The drug is prescribed in the amount of 2 tablets 3 times a day. The daily dose is 1200 mg. The medicine is taken after meals. The tablets are not chewed, but swallowed whole with a sufficient amount of water.

Contraindications for use. The drug is not prescribed in case of hypersensitivity to the drug, severe bleeding and hemorrhages in the eye, hemorrhagic diathesis, ulcerative lesions of the stomach and intestines. The drug should not be used during the acute stage of myocardial infarction.

Side effects. Patients taking the drug may complain of increased blood pressure, tachycardia, irregular heartbeat, bleeding, dizziness and headaches, sleep disorders, hand tremors, gastrointestinal disorders and bowel disorders. Sometimes allergic reactions are observed: skin rash, itching, hyperemia of the skin. Some patients complained of increased sweating and body temperature, visual impairment, and the development of conjunctivitis without apparent cause.

Precautions: The drug should be taken only as prescribed by a doctor under the control of blood counts, as it can cause life-threatening conditions: anaphylactic reactions and aplastic anemia.

To thin the blood in order to improve blood flow in peripheral vessels, the usual "Aspirin" ("Acetylsalicylic acid") is most often used. This drug has anti-inflammatory and antiplatelet effects.

Method of administration and dosage. In case of livedo reticularis not associated with other pathologies, small doses of the drug are prescribed (a quarter of a tablet once a day in the evening). In case of cardiac pathologies, preference is given to the drug "Aspirin cardio". The duration of treatment is determined by the attending physician.

Contraindications for use. The drug is not used to treat patients with acute ulcerative lesions of the gastrointestinal tract, hemorrhagic diathesis, bronchial asthma. Breastfeeding is stopped during treatment with the drug. Do not use the drug from the NSAID category in the 1st and 3rd trimester of pregnancy, as well as in case of hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs.

The drug is also not prescribed to children with acute respiratory infections, since they have a high risk of dangerous complications under the age of 15.

Side effects. Side effects of the drug include: irritating effect on the gastrointestinal tract with the resulting symptoms, including the development of ulcerative processes and iron deficiency anemia. In addition, dizziness, tinnitus (unlikely at low doses), bleeding, urticaria, severe allergic reactions are observed.

An effective and inexpensive drug for strengthening blood vessels from the category of vitamins is considered "Ascorutin". The drug contains vitamins C and P, which are useful for blood vessels.

Method of administration and dosage. Prescribe the vitamin preparation 1 tablet three times a day after meals. Do not chew the tablets, but swallow them whole, washing them down with water (not mineral, which reduces the effectiveness of ascorbic acid, aka vitamin C).

For the prevention of vascular diseases, the drug is taken 2 times a day. Single dose - 1 tablet.

Contraindications for use. Do not use the drug to treat children under 3 years of age, with high blood clotting, in the presence of hypersensitivity to at least one of the components of the drug.

Side effects. Side effects of the drug are very rare. Sometimes during the intake of "Ascorutin" symptoms such as insomnia, headaches, increased blood pressure, nausea, sometimes leading to vomiting, mild allergic reactions are noted.

For the treatment of systemic autoimmune vascular diseases, in which the pattern of livedo vasculitis is detected on the skin, glucocorticosteroids (GCS) are indicated. One of the GCS doctors' favorites is the hormonal drug "Prednisolone".

Method of administration and dosage. The initial dose of the drug is 20 to 30 mg with the possibility of increasing to 100 mg per day. The maintenance dose ranges from 5 to 15 mg. The patient should take two thirds of the daily dose in the morning and one third in the evening.

Contraindications. The drug is not prescribed to patients with severe forms of arterial hypertension, heart failure, after myocardial infarction, diabetes mellitus, hypothyroidism, thyrotoxicosis and Ishchenko-Cushing syndrome, with stage 3 circulatory failure, acute endocarditis, inflammatory kidney pathologies. The drug is prohibited if the patient suffers from psychosis, glaucoma, ulcerative gastrointestinal lesions, osteoporosis, syphilis or acute tuberculosis. Corticosteroids are also contraindicated in the postoperative period, as well as in immunodeficiency states.

It is not advisable to prescribe GCS during pregnancy and in old age, in severe liver and kidney pathologies with impaired function, as well as in the period after vaccination (depending on the vaccine, from 2 to 10 weeks).

Side effects. Since Prednisolone is a hormonal drug, it can provoke the development of obesity, increased hair growth on the body in women, menstrual irregularities, acne, deterioration of bone tissue (fragility), psychoemotional disorders.

In addition, taking the drug may be accompanied by the formation of erosions and ulcers on the mucous membrane of the gastrointestinal tract, and in case of ulcer disease, it may provoke ulcer perforation. Sometimes the drug causes the development of hemorrhagic pancreatitis, which is dangerous due to hemorrhages in the gland.

Taking the drug may contribute to an increase in blood glucose levels, a deterioration in the body's defenses, and an increase in blood viscosity.

Precautions. The drug is addictive. It should be discontinued gradually to avoid such unpleasant consequences as the development of withdrawal syndrome, adrenal insufficiency, exacerbation of the pathology for which GCS were prescribed.

If the patient has infectious pathologies, then treatment with Prednisolone should be carried out in combination with antibiotic therapy.

Folk treatment of livedo reticularis

Treatment of livedo reticularis with folk methods is, first of all, providing heat to the area where the vascular mesh appears. This can be wrapping or a warm bath.

Traditional treatment of vascular disorders also includes traditional recipes that help reduce blood viscosity and improve blood circulation.

Natural freshly squeezed orange juice, which should be consumed half a glass a day, thins the blood well due to its high content of vitamin C.

Sprouted wheat reduces blood viscosity and improves the cardiovascular system. Whole, undamaged wheat grains are washed and covered with water, leaving for several hours. Then the old water is drained and the wheat is sprinkled with fresh water so that the grain does not dry out. The grains are covered with a damp napkin on top. The grains will sprout within 2 days. You need to eat grain with a sprout of about 1-1.5 mm, 1 tablespoon per day. The course of treatment is 1 month.

To strengthen blood vessels, traditional medicine specialists recommend consuming honey with lemon or garlic with lean oil and walnuts. A dish of raisins, dried apricots and prunes, flavored with honey and sprinkled with nuts, will also be useful.

To strengthen blood vessels, it is useful to eat legumes, eggplants, citrus fruits, fruits rich in vitamins C and P, black currants, and, of course, onions and garlic.

With high blood pressure, honey and lemon will come in handy again. You can add viburnum or mineral water to this mixture. You can also prepare a mixture that is infused for 4 hours before use: honey, lemon pulp, carrot and beet juices taken in different quantities, grated horseradish root. You need to use the medicine for blood pressure 1 tbsp. several times a day.

Herbal treatment is effective in treating vasculitis. Medicinal infusions include yarrow (herb), nettle (leaves), knotweed (herb), elderberry (flowers), Japanese pagoda tree (fruit). Calendula (flowers), string (herb), licorice (root) and other medicinal plants will be useful in treating vasculitis.

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Homeopathy

Doctors recommend treating livedo reticularis and various vascular pathologies with homeopathy with a certain degree of caution. Especially when it comes to reducing blood viscosity.

There are many effective and safe folk recipes for blood thinning, which have a less pronounced effect than homeopathic drugs. Remember that for idiopathic livedo, doctors recommend small doses of "Aspirin", which will not cause bleeding from the vessels.

But homeopathy is quite applicable for combating high blood pressure. Barium salts (Baryta carbonica, Barita muariatica in 3 and 6 dilutions) and gold salts will be useful. In addition, Secale and Adrenalinum in 6 and 12 dilutions, Acidum phosphoricum and Nux vomica in 3 and 6 dilutions, Veratrum viride in 3X potency and others that affect peripheral vessels and blood flow in them are prescribed.

But the following homeopathic remedies have a positive effect on the walls of blood vessels: Arnica (potency 3X), Potassium phosphoricum in 6 dilutions and again Nux vomica in 3 or 6 dilutions.

The above-mentioned medications should only be prescribed by a professional homeopathic physician after an up-to-date diagnosis has been made, otherwise the treatment may be ineffective and in some cases even harmful to the patient’s health.

Prevention

Prevention of livedo consists of avoiding hypothermia of the extremities and body, using thermal procedures, and dosed physical activity: running, walking (especially useful is walking barefoot on uneven surfaces, hot sand, alternately on hard and soft surfaces), exercising on exercise bikes to improve heart function.

Regular cleaning of blood vessels is also effective to prevent atherosclerosis. For this, you can use regular boiled water, which you should drink in the morning on an empty stomach in the amount of 1 glass.

You can normalize blood pressure and remove salts from the body that settle on the walls of blood vessels using folk remedies (rosehip tincture, lemon balm infusion, sophora decoction, etc.), which can be consumed instead of tea.

To keep blood vessels normal and avoid the appearance of a marble pattern on the body, which characterizes livedo reticularis, water treatments (ideally a contrast shower) will help, and, of course, proper nutrition, walks in the fresh air, giving up bad habits, regular medical examinations, and careful attention to your health.

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Forecast

Idiopathic livedo reticularis, which is sometimes also called benign, without the addition of livedo vasculitis has a very favorable prognosis and does not affect the health of patients.

The prognosis for symptomatic livedo depends entirely on the pathology that caused the marble pattern to appear on the body, the timeliness of seeking help, the severity of the disease, and compliance with the doctor's orders regarding the underlying disease.