How can acute edema blisters develop as a complication of hereditary angioedema? What are the key symptoms and causes of this rare condition?.

Hereditary Angioedema and Edema Blisters

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of severe swelling, known as angioedema, at various body sites. This condition is typically caused by a deficiency or dysfunction of the C1 inhibitor (C1-INH) protein, which plays a crucial role in regulating the inflammatory response.

In most cases of HAE, patients experience swelling of the skin, abdominal pain, and potentially life-threatening laryngeal edema. However, in some rare instances, the skin swelling associated with HAE can lead to the development of acute edema blisters (AEB) – a unique and unusual manifestation of this condition.

Case Report: Acute Edema Blisters in HAE

The article describes the case of a 47-year-old woman with HAE-C1-INH type 1 who developed multiple blisters on her left forearm during a severe skin swelling episode. A few hours after the onset of the swelling, the patient noticed the appearance of blisters on the affected area, but without any accompanying inflammatory signs or fever.

The patient’s family history revealed a history of potentially fatal laryngeal edema attacks in her father and brother, as well as recurrent skin swellings, abdominal pain, and laryngeal edema in her son. The patient herself had experienced mild recurrent skin swellings, mostly on her forearms, as well as abdominal pain attacks and one mild laryngeal edema episode since the age of 15.

Causes and Characteristics of Acute Edema Blisters

According to the authors, the blisters observed in this case were likely “acute edema blisters” (AEB), which arise from the underlying edema associated with an HAE attack. AEB are an extremely rare complication of HAE, with only a few reported cases in the literature.

AEB are believed to be caused by the high interstitial fluid pressure that leads to the separation of the dermo-epidermal junction, resulting in the formation of subepidermal blisters in the absence of inflammatory signs. These types of blisters are most commonly observed in conditions like chronic venous insufficiency and cardiac edema, but can also occur in severe skin swelling episodes associated with HAE.

Prevalence and Significance of AEB in HAE

In a study of 201 HAE patients with 65,102 skin swellings, only 3 patients (1.5%) reported the development of blisters, with the majority of swellings occurring in the extremities. The authors are aware of only one other case in which a patient experienced recurrent blistering episodes during HAE attacks.

The occurrence of AEB in HAE is an extremely rare phenomenon, and the current case report highlights the need for increased awareness and recognition of this unusual manifestation of the condition. Identifying AEB in HAE patients is important, as it can help differentiate this complication from other potential causes of blistering, such as bullous erysipelas or blistering phytophotodermatosis.

Implications for Management and Future Research

The development of AEB in HAE patients may indicate the severity of the underlying edema and could potentially serve as a marker for more severe attacks. Further research is needed to better understand the pathophysiology and prevalence of this rare complication, as well as its implications for the management and treatment of HAE.

In the meantime, healthcare providers should be aware of the possibility of AEB in patients with HAE and should closely monitor these individuals for the development of blisters during acute edema episodes. Prompt recognition and appropriate management of this rare complication are essential to ensure the best possible outcomes for HAE patients.

Conclusion

The case report described in this article highlights the rare occurrence of acute edema blisters as a complication of hereditary angioedema. While AEB are an unusual manifestation of HAE, they can provide valuable insights into the underlying pathophysiology of the condition and may have implications for the management and treatment of affected individuals. Further research is needed to better understand the prevalence and significance of this rare complication, but increased awareness among healthcare providers is essential to ensure timely recognition and appropriate care for HAE patients.

Acute Edema Blisters on a Skin Swelling: An Unusual Manifestation of Hereditary Angioedema | HTML

Content » Vol 96, Issue 4

José Fabiani1 and Konrad Bork2

1Instituto Argentino de Alergia, Buenos Aires, Argentina, and 2Department of Dermatology, Johannes Gutenberg University, Langenbeckstr. 1, DE-55131 Mainz, Germany. E-mail: [email protected]

Accepted Sep 30, 2015; Epub ahead of print Oct 6, 2015

In most patients, hereditary angioedema (HAE) is caused by a deficiency of functionally active C1 inhibitor (C1-INH) in plasma (HAE-C1-INH), due to mutations of the C1-INH gene (1). HAE-C1-INH is clinically characterized by recurrent episodes of edema at various body sites, followed by disease-free intervals of variable duration. Skin swellings, abdominal pain attacks and laryngeal attacks are the most frequent symptoms. Laryngeal attacks are potentially fatal and can lead to airway obstruction and death by asphyxiation (2). We report here a patient with HAE-C1-INH who developed blisters on her skin swelling as a rare complication of HAE-C1-INH.

CASE REPORT

A 47-year-old Caucasian woman attended the clinic with severe swelling of her left forearm. A few hours after onset of the swelling multiple blisters developed on the skin at the site of the swelling (Fig. 1). The lesions were not accompanied by inflammatory signs or fever. There were no blisters on other body parts and the patient had no subjective complaints. The regional lymph nodes were not painful or enlarged. Three days later, the swelling had completely subsided, but remnants of the blisters were visible for approximately one week.

Fig. 1. Multiple blisters on a skin swelling of hereditary angioedema.

The patient’s family history revealed that her father and brother had died of asphyxiation from laryngeal edema and that her son had had recurrent skin swellings, abdominal pain attacks, and laryngeal edema. The patient had previously experienced mild recurrent skin swellings, mostly located on her forearms, several abdominal pain attacks, and one mild laryngeal edema. Initial symptoms started at the age of 15 years and since then, she had experienced one attack every 2 or 3 years.

Laboratory results showed C1 inhibitor protein 8.9 mg/dl (normal 15–35 mg/dl), C1 inhibitor activity 25% (normal 70–130%), and C4 9 mg/dl (normal 20–40 mg/dl). Consequently, HAE-C1-INH type 1 was diagnosed.

DISCUSSION

In our patient, the blisters followed a massive skin swelling and were not typical for a bullous erysipelas or a blistering phytophotodermatosis with lymphangitis. Since the blisters were confined to the site of the skin swelling, we assume that they were “acute edema blisters” (AEB), arising from the underlying edema of an HAE-C1-INH attack. This is an extremely rare presentation of HAE-C1-INH. In a study of HAE symptoms, 196 (97.5%) of 201 patients with 65,102 skin swellings reported a total of 59,095 (90.8%) swellings at the extremities (3). Of these, only 3 patients (1.5%) with more severe swelling reported blister formation: 2 patients had blisters in the crook of the elbow and one patient developed blisters at the instep, one day after onset of the attack. As in the case described here, all 3 patients experienced only one episode of blistering. We are aware of only one case in which a patient’s HAE-C1-INH skin swellings were accompanied by blisters on more than one occasion (4). Only recently, another patient with HAE-C1-INH was described, who developed painful blistering upon acute edema exacerbation (5). In this case, however, the blisters were not located at the site of the skin swelling.

AEB are caused by high interstitial fluid pressure that leads to the separation of the dermo-epidermal junction, resulting in subepidermal blister formation in the absence of inflammatory signs. AEB have only been reported in patients with severe swelling and are most frequently observed on the lower leg (“hydrostatic bullae”). They are usually associated with chronic venous insufficiency and edema due to cardiac insufficiency (6). Blistering sometimes occurs in cutaneous mastocytomas. The current report shows that AEB may occur due to severe skin edema of HAE-C1-INH.

REFERENCES

1. Nzeako UC, Frigas E, Tremaine WJ. Hereditary angio­edema: a broad review for clinicians. Arch Intern Med 2001; 161: 2417–2429.

2. Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol 2012; 130: 692–697.

3. Bork K, Meng G, Staubach P, Hardt J. Hereditary angio­edema: new findings concerning symptoms, affected organs, and course. Am J Med 2006; 119: 267–274.

4. Fernandez Romero D, Di Marco P, Malbran A. Acute edema blisters in a hereditary angioedema cutaneous attack. Allergol Immunopathol (Madr) 2008; 36: 182–183.

5. Wiesen J, Gonzalez-Estrada A, Auron M. Postangioedema attack skin blisters: an unusual presentation of hereditary angioedema. BMJ Case Rep 2014 Apr 10; 2014. pii: bcr2013201482.

6. Bhushan M, Chalmers RJ, Cox NH. Acute oedema blisters: a report of 13 cases. Br J Dermatol 2001; 144: 580–582.

This work is licensed under a Creative Commons Attribution-NonCommercial 4. 0 International License.

Blisters | AAFP

RAYMOND T. KUWAHARA, M.D., Oklahoma University Health Sciences Center, Oklahoma City, OK

Am Fam Physician. 2004;70(6):1125-1126

A 50-year-old man in the intensive care unit has large bullae bilaterally on his inner thighs (see accompanying figure). The patient was admitted two days before the onset of the blisters with congestive heart failure and renal failure. On the day before the dermatology consult, the patient was started on intravenous vancomycin for presumed bilateral lower extremity cellulitis. The blisters were tense, filled with clear fluid, and measured about 1 to 3 cm in size.

Question

Based on the patient’s history and physical examination, which one of the following is the correct diagnosis?

A. Bullae secondary to edema.

B. Bullous pemphigoid.

C. Pemphigus vulgaris.

D. Herpes zoster.

E. Fixed drug reaction.

Discussion

Answer is A: Bullae secondary to edema. Patients with fluid overload may present with blister formation, especially on the extremities such as occurred with this patient. When the cause of the underlying edema is treated, the blisters subside. Blisters that form because of edema contain sterile fluid. Because of their thin roof, they usually break within a few days. Once the fluid imbalance is corrected, these blisters resolve without recurrence.¹ If the blisters are located on a distal portion of the lower extremities, elevation of the legs can reduce the edema and subsequent blister formation.

Bullous pemphigoid is an autoimmune disease that typically occurs in older patients. Men are affected more commonly than women. Blisters appear on the extremities and intertriginous areas first and later involve the trunk. Intact blisters tend to outnumber erosions in pemphigoid, while the reverse is true of the more superficial blisters occurring in pemphigus.

Pemphigus vulgaris is another autoimmune blistering disease. Patients present with painful bullae that appear on normal skin without surrounding inflammation.² Lesions often start in the oral mucosa and may precede other cutaneous lesions by several weeks or months. The blister can be extended easily into adjacent skin with gentle pressure (Nikolsky’s sign). Because pemphigus vesicles are thin-roofed, erosions typically outnumber intact blisters. After a blister breaks, the shallow erosion in the skin may take weeks or months to heal.

Varicella zoster virus is a herpes family virus commonly known as chickenpox. The recurrence of varicella zoster is known as herpes zoster, which is recognized by the unilateral dermatomal distribution of vesicles. The large size and bilateral distribution of the blisters in this case would make zoster unlikely.

A fixed drug reaction typically presents with bulla formation on an erythematous base. This fixed reaction reappears in the same site each time the causative drug is ingested.³ Salicylates, nonsteroidal anti-inflammatory drugs, barbiturates, tetracycline, and sulfonamides are among the drugs most commonly cited as causes of fixed drug reactions. The most common cutaneous reaction associated with vancomycin is an urticarial rash, but it also may cause red-man syndrome, toxic epidermolysis necrolysis, or Stevens-Johnson syndrome.

The editors of AFP welcome submissions for Photo Quiz. Guidelines for preparing and submitting a Photo Quiz manuscript can be found in the Authors’ Guide at https://www.aafp.org/afp/photoquizinfo. To be considered for publication, submissions must meet these guidelines. Email submissions to [email protected].

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of Photo Quiz published in AFP is available at https://www.aafp.org/afp/photoquiz. 

Swelling of the legs – the reasons why the right or left leg, calves swell, swell, what to do?

A fairly common symptom that occurs due to the accumulation of a large amount of fluid in the intercellular space of the tissues of the lower extremities.

Contents of the article

Causes and types of edema of the lower extremities
Lymphedema and tests for its recognition

Patients often come to our clinic complaining of edema of the lower extremities. It is not always a symptom of varicose veins. Consider the causes of its occurrence, as well as tests that will help identify lymphatic edema.

Causes and types of edema of the lower extremities

Edema is a symptom that may be associated with deep vein thrombosis or thrombophlebitis. There is chronic edema on the background of varicose veins, when we see that the veins in the legs are dilated and there is swelling of the legs, which manifests itself at the end of the day.

Edema of the legs is of two types: symmetrical – swelling of two limbs and asymmetric. The second occurs on one limb and is often accompanied by acute pain, may be associated with venous disease. It is caused by either deep vein thrombosis or thrombophlebitis. In advanced cases, chronic edema occurs against the background of varicose veins, when we see altered varicose veins and edema, which can appear as traces of a sock gum by the end of the day.

The main causes of swelling of the legs include:

• diseases of the veins of the lower extremities
• heavy physical exertion;
• ➡️ standing or sitting for a long time;
• ➡️ kidney disease;
• ➡️ hormonal fluctuations in women ;
• ➡️ diseases of the joints;
• ➡️ purulent processes;
• ➡️ thyroid dysfunction;
• ➡️ traumatic injuries;
• ➡️ heart problems.

Edema may occur regularly or periodically, accompanied by heaviness in the legs, fever of the whole body or the affected area. At the first symptoms, you should consult a doctor.

Lymphedema and tests to detect it

Lymphedema presents as persistent lymphatic swelling of the soft tissues of the affected area and most commonly occurs towards the end of the day. It is primary and secondary. There are several tests that will help identify such a disease:

• Measuring the circumference of the ankles before bed and in the morning. If the circumference changes, becomes larger in the evening, and disappears in the morning – this is the first signal for the development of lymphedema. If at the same time there are no visible varicose veins and the edema manifests itself symmetrically, then the lymphologist will deal with the problem.
• The second test – you need to examine the lower and upper limbs to detect local swelling of the ankle and wrist joints. The test is done in the morning and before bed. If the swelling does not subside overnight, then the disease is progressing.
• Finger pressure along the course is larger than the tibia. If the hole does not remain, and the leg is enlarged, then the leg is very swollen, lymphedema develops. If the fossa remains and does not pass for some time, then this is a cardiological edema, which is associated with poor functioning of the heart muscle.

We recommend that you keep a diary and record the circumference of the right and left ankle at different times, as well as the circumstances in which the swelling occurred, such as hot weather. This will help to identify under what circumstances edema appeared and what it is connected with. The reason for the development of lymphedema can be a constant static load when a person is in a state of sitting or standing. At the slightest sign of the appearance of any edema, it is necessary to consult a phlebologist, lymphologist or therapist.

IMPORTANT : Do not self-medicate.

We offer modern methods for diagnosing edema by the best specialists. The clinic uses high-tech equipment, we can perform laboratory tests, which allows us to form an optimal treatment plan.

Causes of swelling of the legs

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FAQ

➡️ Is it possible to completely get rid of varicose veins?

The disease is chronic. Various methods and preparations help to remove its symptoms, however, if the patient already has venous “knots”, then the vascular wall has been irreversibly changed and nothing can change them. In this case, surgical treatment is prescribed. The best that can be achieved is to contain the further development of the disorder and avoid the occurrence of complications (trophic ulcers, conditions that can lead to disability and even death). Today, such methods have become popular: sclerotherapy, laser, physiotherapy, hirudotherapy, drug treatment.

➡️ What threatens varicose veins?

Varicose veins can lead to a number of complications and other diseases. Telangiectasia – swelling, burning, nocturnal cramps and loss of sensation. Thrombophlebitis is an acute inflammation of the walls of blood vessels, which can cause a violation of the structure of the blood and the speed of its circulation. Clots turn into solid blood clots, which can break away from the vessels and clog the lumen of the vein. Deep vein thrombosis also develops, trophic ulcers can form.

➡️ What kind of disease is thrombophlebitis?

Thrombophlebitis is a disease of the circulatory system, which manifests itself in the form of inflammation of the walls of the veins with the formation of so-called blood clots in a short time. As a result, the lumen of the bloodstream is significantly reduced, which leads to a violation of the movement of the blood flow. The surrounding veins also become inflamed, which is expressed by their redness.

what it is, how it occurs, treatment

Blisters on the legs is a rather unpleasant phenomenon both from the aesthetic and physical sides.

They can appear anywhere on the foot and cause a lot of discomfort.

Contents:

• What is it?
• Causes
• First actions upon occurrence
• Method of treatment
• Pharmaceutical drugs
• Folk remedies
• Features of therapy of certain types
• When is medical assistance needed?
• Prevention

What is it?

A blister is a swollen piece of the upper layer of the skin that occurs when it rubs against the material of the shoe.

This is a neoplasm in the form of an inflated bubble, dense to the touch, having a different shape.

They contain liquid, so they spring back slightly when pressed. On the feet, blisters often appear on the feet, between and on the toes.

Sizes may vary : small bubbles to fairly large bubbles.

There are cases when numerous blisters merge into one large pillow. The color of the bubbles is from pale pink to yellowish white with pink edges.

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Causes

The true cause of their appearance on the legs can be determined by a dermatologist. The most common reasons for their formation are the following:

• Uncomfortable shoes – tight or too loose, made of rough materials or with hard elements protruding inside. From the friction of the skin on such shoes, blisters are formed.
• Allergic reactions to food, drugs or chemicals. Such blisters are cured after the use of antihistamines.
• Fungal infection . Its presence can be indicated by a large number of small bubbles on the feet, which at the same time are very itchy.

Sometimes a blister that appears suddenly may just as suddenly disappear. But often it causes a lot of inconvenience or begins to hurt, itch. Worst of all, when it breaks through and begins to fester.

Sometimes the blister begins to itch unbearably. This may be the case if it is a consequence of infection with a fungus or an allergic reaction. It is not recommended to scratch it, as this can damage the shell and cause infection. Then suppuration will occur in its place, and the problem will worsen.

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First steps when

appears It is not recommended to pierce them to avoid infection.

If the formation is small and it is possible to preserve its integrity by protecting its area from the material of the shoe, then it is better to wait until it passes naturally.

When the bubble is of impressive size, it most often causes inconvenience, and most likely it will not be possible to save it without injuring it.

In this case, it is more expedient to pierce his until it collapses on its own. With such an outcome, dirt can get into it, and it will become inflamed.

Wash feet and hands thoroughly before use. Prepare a needle disinfected with alcohol or burned. Wipe the blister with alcohol and make a small puncture at the base, closer to the intact skin. Squeeze out all the liquid from the bubble.

IMPORTANT Do not cut off the top layer of skin from the blister, as the wound will take a long time to heal.

Press the skin against the wound, it will help protect the inner surface from infection . Seal the sore spot with adhesive tape. If the blister area is large, apply a gauze bandage.

WARNING The area under the dressing must be constantly dry, otherwise the area will become inflamed.

Change the bandage daily, and if possible twice a day, to avoid the slightest chance of getting a blister inside it.

If possible, the bandage should be removed: at night or when you are at home, and it is possible to walk without shoes. So healing will happen faster, as the skin will dry out. A blister that is completely dry and well protected from infection will soon dry out and fall off on its own. Under it, you will find perfectly healthy skin.

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Method of treatment

To choose method of treating formation, first of all, it is necessary to find out the cause of its formation. If it is a fungus or an allergic reaction, the underlying cause must be treated first by consulting a doctor.

Blisters caused by rubbing against uncomfortable shoes can be treated in two ways:

This healing patch is designed specifically for the treatment of watery blisters. It contains and gradually releases a special gel from its surface, which relieves pain and protects the skin during treatment.

Herbal bath with herbal ingredients, soothes blisters and calluses.

Aloe Vera Foot Cream

Lavender Oil

Levomecithin Ointment

Panthenol Ointment

Gehwol Assortment

Fusscraft foot bath

They can appear when a wart is removed with nitrogen, frostbite, and other cases. Learn about whether blisters that form on the skin with fluid can be popped.

On the body blisters that itch can appear in different places: on the back, eye, ear, buttocks, on the penis and even in the hair on the head.

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Folk remedies

• Trays with weak concentration of potassium permanganate or salt. They take 15 minutes.
• Tea tree oil. Used to lubricate the blister.
• Film from under the shell of a raw egg. It is glued to the bubble, and it disappears in two or three days.
• Compress with string decoction. 4 tablespoons of leaves are steamed in a water bath for 30 minutes, cooled, a napkin is moistened with a decoction and applied to a blister.
• Mole hair ring (or any other animal hair). A very exotic way, but, according to reviews, quite effective. Wool should be laid around the bubble, and it will protect it from rupture and infection of the inner surface.

IMPORTANT Do not apply pressure to the blister. If it is possible not to injure him, it is better to wait for the natural disappearance.

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Peculiarities of therapy of certain types

The method of treatment of blisters depends on where they are localized and on their condition:

• Liquid blisters on the legs;

They are treated with special patches, which are a gel-filled pad.

Its purpose is to protect against neoplasm and prevent rupture and infection. Such a patch is glued on a bubble smeared with greenery. The period of use of the funds depends on the state of education. You should wait for the complete disappearance of the bubble.

• For swelling of the legs;

Slight swelling of the legs in the evening is normal. Therefore, consider this, and if you have to be on your feet for a long time, take the most free shoes with you to change your shoes. This will help you prevent skin pressure and blistering. If edema is the result of any diseases, then it is necessary to treat them first of all. For the period of relief of symptoms of swelling, use protective patches and pads to help protect the skin of the legs.

• For diabetes;

This disorder can cause blisters to form on the skin, similar to burn blisters. They can appear on the toes, feet, legs. Direct treatment of these formations is not required. The main task in this case is the systematic control of blood sugar levels. If the sugar is normal, the blisters will disappear on their own without additional treatment.

• Blister on foot;

The latest development of the German company Genvol – Oval protective patch will save them from them. It is glued to the problem area of ​​the foot and protects it from excessive friction and pressure. This patch is especially recommended for lovers of high heels.

• Blood blister;

Appears if friction has occurred on the area where the blood vessel is located.

It occurs on the fingers or heels in places of greatest contact with the rough material of the skin.

If you feel pain in a particular area while putting on your shoes, it is necessary to protect this area of ​​the skin in advance, without waiting for the formation of a blood blister. Put on a protective patch or put on socks to help avoid irritation.

Foot hygiene is very important in case of blood formations to prevent accidental infection of the wound. If a blood blister accidentally bursts, immediately disinfect the affected area and cover it with a bandage. In no case can the top film be removed, press it against the bubble area and seal it with a plaster.

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When is medical assistance needed?

An emergency call to a doctor is inflammation at the site of a blister. Symptoms of the onset of inflammation are the following signs:

• Severe, ever-increasing pain in the area of ​​education.
• Redness or fever around the skin.
• Discharge from a blister of blood or pus.
• Increased body temperature.
• Inflammation of the lymph nodes in the body.
• Suspicion of fungus. Numerous small bubbles on the fingers and between them testify to it. In this case, there is severe itching.

If you notice even one of these signs, urgently see a doctor ! At the hospital, your blister will be opened under sterile conditions, disinfected, and given anti-inflammatory drugs.

If you are unable or unwilling to see a doctor for treatment, deciding to treat them yourself, remember the following:

• Do not allow the development of a yellow-brown blister that is too hard.
• Control treatment time. If the recovery is delayed, it is better not to take risks and still contact the doctors.
• Before using pharmacy products, carefully study the instructions and in no case violate them.

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Prevention

If blisters form on your feet that are not associated with uncomfortable or low-quality shoes, first of all, you need to analyze and eliminate the causes of their occurrence .

• Review your diet if it is a reaction to eating any foods.
• Take antifungal medication and try to prevent infections in the future.
• Avoid contact with cosmetics that can cause allergic reactions on the skin of the feet.

Blisters caused by friction should be prevented by choosing the right shoes and using protective equipment:

• Choose shoes that fit. It should not be cramped, and at the same time it should not be large. The material should fit snugly to the foot, but not squeeze it.
• Always break in a new pair of shoes at home with socks before wearing them outside.
• Use protective pads and special corn plasters if you are going to be outdoors for a long time in your shoes.
• Try to wear closed shoes with socks made from natural materials.
• Take care of the skin of your feet, use emollient creams regularly. The softer the skin on the legs, the less likely it will be scuffed.
• In case of excessive sweating of the feet, be sure to use special products that relieve this problem. A very effective remedy is baby powder. Also in this case, you should not wear shoes on bare feet.

IMPORTANT Synthetic socks should not be worn in case of excessive sweating of the feet. Wear only cotton socks that will absorb excess fluid.

• Use natural leather insoles with special ventilation holes in your shoes, this will help prevent blisters on your feet.
• Blisters on the heels will help prevent the use of special gel pads that soften the impact of the heel on the shoe. Their use is necessary if you have planned a long walk or outdoor activity.