Hereditary angioedema with C1Inh deficiency

What it is

From: Orphanet

A rare hereditary angioedema characterized by potentially life-threatening episodes of subcutaneous and/or submucosal edema without urticaria, associated with C1 esterase inhibitor (C1-INH) deficiency. Hereditary angioedema (HAE) type 1 is caused by quantitative, HAE type 2 by qualitative defects of C1-INH. The two subtypes are clinically indistinguishable. Patients may present at any age (but most commonly in childhood) with recurrent attacks of nonpitting edema of the skin, severe abdominal symptoms such as pain and swelling, and/or respiratory distress due to upper respiratory airways involvement. Genital, bladder, muscle, or joint swelling may occur in some cases.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abdominal pain · Frequent (79-30%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.

Angioedema · Frequent (79-30%)

Rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues of the skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue during a period of minutes to several hours. The swelling can also occur elsewhere, typically in the hands. Angioedema is similar to urticaria, but the swelling is subcutaneous rather than on the epidermis.

Decreased circulating C1-esterase inhibitor concentration · Frequent (79-30%)

Decreased concentration of C1-esterase inhibitor (C1INH) in the blood circulation.

Decreased circulating complement C4 concentration · Frequent (79-30%)

Concentration of the complement component C4 in the blood circulation below the lower limit of normal.

Diarrhea · Frequent (79-30%)

Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.

Erythema marginatum · Frequent (79-30%)

An erythematous (pink-red, depending on the skin color of the affected individual) macule that spreads peripherally and coalesces to form polycyclic or serpentine patches or plaques. Lesions occur in crops over days to weeks and are evanescent. The rate of migration is 2 to 12 mm over a period of a few hours. Erythema marginatum tends to affect the trunk more than the extremities and to not be accompanied by pruritus.

Genital edema · Frequent (79-30%)

A buildup of fluid that causes swelling in the soft tissues of the genital area.

Laryngeal edema · Frequent (79-30%)

An abnormal accumulation of fluid and swelling in the tissues of the larynx.

Nausea and vomiting · Frequent (79-30%)

Nausea is a commonly encountered symptom that has been defined as an unpleasant painless subjective feeling that one will imminently vomit. Vomiting has been defined as the forceful expulsion of the contents of the stomach, duodenum, or jejunum through the oral cavity. While nausea and vomiting are often thought to exist on a temporal continuum, this is not always the case. There are situations when severe nausea may be present without emesis and less frequently, when emesis may be present without preceding nausea.

Non-pitting edema · Frequent (79-30%)

Non-pitting edema occurs when excess fluid builds up in the body causing swelling that does not indent when pressure is applied. It usually occurs in the limbs, and often results from underlying medical conditions affecting lymphatic system function.

Pain · Frequent (79-30%)

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

Pharyngeal edema · Frequent (79-30%)

Abnormal accumulation of fluid leading to swelling of the pharynx.

Serpiginous cutaneous lesion · Frequent (79-30%)

A skin lesion with a snake- or serpent-like distribution.

Skin rash · Frequent (79-30%)

A red eruption of the skin.

Other findings in the same source

From: Orphanet

Additional reported features include Facial edema (Frequent (79-30%)); Joint swelling (Frequent (79-30%)); Muscular edema (Frequent (79-30%)); Asthenia (Occasional (29-5%)); Fatigue (Occasional (29-5%)); Headache (Occasional (29-5%)); Paresthesia (Occasional (29-5%)); Episodic upper airway obstruction (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adult; Elderly

Inheritance in the source

From: Orphanet

Not applicable

Frequency and the population described

From: Orphanet

Reported case(s): 51.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Which doctor should you see?

The suggested department for discussing Hereditary angioedema with C1Inh deficiency is Rheumatology, with a rheumatologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Are the findings inflammatory, structural or due to another mechanism?
• Is there evidence that other organs need assessment?
• How will function and any treatment-related risks be monitored?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hereditary angioedema with C1Inh deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.