What is Lipoid Proteinosis?
Lipoid Proteinosis (LP), also known as hyalinosis cutis et mucosae, was first identified by Urbach and Wiethe in 1929. LP is a rare skin disorder caused by an excess of a certain type of protein, which resembles a substance called hyaline, collecting in various parts of the body. This disorder affects not only the skin and mucus membranes but can also lead to a variety of other symptoms affecting the nervous system, mental health, and digestion.
What Causes Lipoid Proteinosis?
Lichen planopilaris (LP) is caused by specific changes, or mutations, to a gene called the extracellular matrix protein 1 (ECM1). This gene lives on chromosome 1q21 in our bodies. Most of these mutations alter the ECM1 gene’s instructions, resulting in a shortened or “truncated” version. This gene is critical because it provides the blueprint for proteins that keep skin firmly attached and support other important functions in the body.
However, because this gene can be read in different ways (a process called splicing) and has many possible mutations, there are several types of LP, each with its own distinct characteristics.
It’s important to note that LP is inherited, which means it’s passed down from parents to their children. It follows a pattern known as autosomal recessive inheritance. In this case, the child must inherit one copy of the mutated gene from each parent to get the disease. That’s why LP often occurs in families, and is more common in children whose parents are related.
Risk Factors and Frequency for Lipoid Proteinosis
LP, or Lichen Planus, is a rare condition that affects people all over the world. However, it has only had about 400 reported cases in medical studies. Both men and women are equally likely to have LP. Interestingly, South Africa’s Namaqualand region has the most LP patients who share a common genetic mutation, hinting that this disease may have originated from a common ancestor. LP seems to be more prevalent in countries where marriages between relatives are more common.
Signs and Symptoms of Lipoid Proteinosis
The first sign people often experience with Lipoid Proteinosis (LP) is a weak or hoarse cry due to a build-up of a jelly-like substance on the vocal cords. This can progress to a persistent husky voice, and in certain cases, even cause difficulties in breathing.
Early on, skin abnormalities might also emerge, usually starting with blisters or small injuries that may bleed. They often appear on areas where there is friction or trauma, especially on the face and around the mouth. These eventually heal, leaving prominent, acne-like scars. The skin may gain a thick, waxy texture with a yellowish tint over time. In some cases, there could be “beaded” bumps along the eyelid margin, a characteristic symptom seen in about half of the patients. Other skin symptoms include rough patches, lumps, or overgrown skin at sites of trauma.
The infiltration of the jelly-like material throughout the mouth and upper digestive tract can result in a bumpy appearance in the mouth, yellow nodules on the lips, and vegetative lesions at the corners of the mouth. If the disease progresses, there can be frequent respiratory infections, dental cavities, and inflammation of glands due to obstruction by the deposits.
The impact of LP on the nervous system can be severe; symptoms can range from epilepsy, muscle cramps, memory loss, behavioural changes, to even hallucinations. Accumulation of calcified deposits in the brain is a distinctive feature which can occur without presenting symptoms. A common finding in medical imaging is comma-shaped calcification in parts of the brain responsible for processing emotions and memories. This effect becomes more common in patients who are older than 10 and those with a longer disease duration.
Lastly, rare cases have documented deposits throughout the digestive tract, which have the potential to cause complications such as gastrointestinal bleeding.
Testing for Lipoid Proteinosis
If you’re experiencing symptoms of a condition called Lichen Planus (LP), your doctor might ask about any family members who’ve had the same symptoms. This is because LP is often passed down through families in what we call an ‘autosomal recessive’ pattern. The diagnosis of LP involves looking at your family history, your symptoms, and the results of skin tests. However, the only way to confirm LP is by identifying a change in a specific gene called ECM1.
You might also need to see a specialist, such as an ear, nose, and throat doctor (otolaryngologist), if LP is affecting your breathing. Neurologists (nerve doctors) and psychiatrists (mental health doctors) may also need to get involved if LP is causing neurological or mental health symptoms. They may order advanced imaging tests, like a CT scan or an MRI, to get a detailed view of your brain.
How often you need additional check-ups will depend on your specific situation. In general, those with LP should get regular dental, skin, and eye check-ups because LP can affect these areas of the body.
Treatment Options for Lipoid Proteinosis
While there’s no go-to treatment method for Lichen Planus (LP), which is a skin disease, various treatments might help depending on the specific symptoms and whether the patient wishes for improved cosmetic outcomes.
Systemic retinoids are medications often used to treat skin issues. Two types, called acitretin or etretinate, might reduce different symptoms on the skin and inside the voice box by lessening the build of certain substances that cause damage in the skin. Some reports have shown that long-term therapy with acitretin resulted in healed skin lesions, decreased tongue size, improved voice quality, and softened skin nodules. Interestingly, some patients saw improvements in voice quality without any noticeable improvements to the skin.
Results have been conflicting regarding the effectiveness of a treatment called dimethyl sulfoxide (DMSO) for reducing skin lesions and hoarseness. Another treatment called D-penicillamine has reportedly improved these symptoms in certain case studies.
For patients who are experiencing voice changes due to vocal cord involvement, procedures using microlaryngoscopy and a carbon dioxide (CO2) laser can be successful. These procedures can, however, lead to tissue growth, fibrosis, and the requirement for further treatments. As a result, some experts recommend that surgery should only be considered in severe cases where the patient’s ability to breathe is affected.
If patients want to reduce the visibility of their scars and other skin changes, then cosmetic procedures can be used. These might include CO2 laser treatment, dermabrasion (a skin-resurfacing technique), blepharoplasty (a surgical modification of the eyelid), and the use of an erbium-doped yttrium aluminum garnet laser.
Management of the neurological and psychological aspects of Lichen Planus needs to be personalized to each patient. Certain anti-seizure medications can help control the frequency and intensity of seizures, while anti-psychotic medications can help manage behavioral changes and psychosis associated with this condition.
What else can Lipoid Proteinosis be?
Different patients might have different possible diagnoses based on their symptoms. Let’s explore some of the potential conditions doctors might consider:
When dealing with skin problems, consider:
- Herpes simplex infection
- Impetigo
- Epidermolysis bullosa
- Erythropoietic protoporphyria
- Lichen myxedematosus
- Systemic amyloidosis
- Nodular localized cutaneous amyloidosis
- Colloid milium
- Hyalinosis
- Xanthomas
- Scleromyxedema
- Leprosy
- Hydroa vacciniforme
- Incontinentia pigmenti
For issues of hoarseness, doctors might think about:
- Laryngitis
- Laryngotracheitis
- Laryngotracheobronchitis
- Vocal cord nodules
- Gastroesophageal reflux disease
- Vocal cord polyps
- Laryngeal hemangiomas
- Laryngeal cysts
- Vocal cord paralysis
- Vocal cord hypertrophy
If a patient has an enlarged tongue, the following diagnoses might be considered:
- Systemic amyloidosis
- Congenital Hypothyroidism
- Myxedema
- Acromegaly
Lastly, for patients presenting with mesial temporal lobe calcification, these conditions might come to mind:
- Fahr’s disease
- Calcified glioma
- Raine syndrome
- Healed herpes encephalitis
- Dystonia
What to expect with Lipoid Proteinosis
Lymphangioma usually follows a harmless but progressive path that doesn’t shorten a person’s life. However, complications can arise if it obstructs the respiratory system or affects the central nervous system (the brain and spinal cord). These complications could potentially be life-threatening or cause significant health issues.
Possible Complications When Diagnosed with Lipoid Proteinosis
LP, or light chain deposition disease, can lead to a variety of health issues because of hyaline, a kind of substance, building up in the skin, inner lining of the body, and multiple organs. Some of the most serious complications include blocked airways, seizures, and spontaneous bleeding in the central nervous system (CNS). Hyaline can also accumulate in the small bowel and lead to gastrointestinal bleeding.
Additionally, if the patient undergoes surgery on the vocal cords or larynx, they may experience complications. These can include conditions such as bleeding, infection, and scarring of the vocal cords. The latter can change the quality of the voice and sometimes necessitate further surgery.
Lastly, patients managing their disease with systemic medicines like anti-psychotic, anti-epileptic, and dopamine-modifying agents may experience various side effects specific to those drugs.
Possible Complications:
- Airway obstruction
- Seizures
- Spontaneous CNS hemorrhage
- Gastrointestinal bleeding
- Bleeding during surgery
- Infections after surgery
- Vocal cord scarring
- Drug-specific side effects
