Cutis laxa or pachydermatocele is a group of rare

connective tissue disorder A connective tissue disease (collagenosis) is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds togeth ...

s in which the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

becomes inelastic and hangs loosely in folds.

Signs and symptoms

It is characterised by skin that is loose, hanging, wrinkled, and lacking in elasticity. The loose skin can be either generalised or localised. Biopsies have shown reduction and degeneration of dermal elastic fibres in the affected areas of skin. The loose skin is often most noticeable on the face, resulting in a prematurely aged appearance. The affected areas of skin may be thickened and dark. In addition, the joints may be loose ( hypermobile) because of lax

ligament A ligament is the fibrous connective tissue that connects bones to other bones. It is also known as ''articular ligament'', ''articular larua'', ''fibrous ligament'', or ''true ligament''. Other ligaments in the body include the: * Peritoneal li ...

s and

tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its ability ...

s. When cutis laxa is severe, it can also affect the internal organs. The

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...

(supravalvular pulmonary stenosis),

intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...

s, or

arteries An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...

may be affected with a variety of severe impairments. In some cases,

hernia A hernia is the abnormal exit of tissue or an organ (anatomy), organ, such as the bowel, through the wall of the cavity in which it normally resides. Various types of hernias can occur, most commonly involving the abdomen, and specifically the gr ...

s and outpouching of the bladder can be observed. Patients can also present with whites of the eyes that are blue.

Causes

In many cases, cutis laxa is inherited.

Autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

, and X-linked recessive forms have been described, but acquired forms also occur. Cutis laxa is associated with deficient or absent

elastin Elastin is a protein that in humans is encoded by the ''ELN'' gene. Elastin is a key component of the extracellular matrix in gnathostomes (jawed vertebrates). It is highly elastic and present in connective tissue allowing many tissues in the bod ...

fibers in the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...

. This can be related to decreased

synthesis or structural defects in the

. Cutis laxa may be caused by mutations in the genes: ''ELN'', '' ATP6V0A2'', ATP7A, ''

FBLN4 EGF-containing fibulin-like extracellular matrix protein 2 is a protein that in humans is encoded by the ''EFEMP2'' gene. A large number of extracellular matrix proteins have been found to contain variations of the epidermal growth factor (EGF) do ...

'', ''

FBLN5 Fibulin-5 (also known as DANCE (developmental arteries and neural crest epidermal growth factor (EGF)-like)) is a protein that in humans is encoded by the ''FBLN5'' gene. Function The protein encoded by this gene is a secreted, extracellular m ...

'', and ''

PYCR1 Pyrroline-5-carboxylate reductase 1, mitochondrial is an enzyme that in humans is encoded by the ''PYCR1'' gene. This gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may al ...

''. A related neurocutaneous syndrome may be caused by mutations in the gene ''ALDH18A1'' (''P5CS''). Cutis laxa may also be seen in association with inherited connective tissue disorders such as

Ehlers–Danlos syndromes Ehlers–Danlos syndromes (EDS) are a group of 13 genetic connective-tissue disorders in the current classification, with the latest type discovered in 2018. Symptoms include loose joints, joint pain, stretchy velvety skin, and abnormal scar fo ...

. Another syndrome associated with cutis laxa is Lenz-Majewski syndrome which is due to a mutation in the phosphatidylserine synthase 1 (

PTDSS1 Phosphatidylserine synthase 1 is a protein that in humans is encoded by the PTDSS1 gene. Function The protein encoded by this gene catalyzes the formation of phosphatidylserine from either phosphatidylcholine or phosphatidylethanolamine. Phos ...

) gene. In contrast, acquired cutis laxa often has a triggering event such as

urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

, drugs (such as

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

) or

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s. Acquired cutis laxa may also be immunologically mediated, as it can involve dermal deposit of

immunoglobulins An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

and it can occur with

autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

s. Acquired cutis laxa has been associated with granular

immunoglobulin A Immunoglobulin A (Ig A, also referred to as sIgA in its secretory form) is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other ty ...

deposits as well as abundant

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

s. One hypothesis for the cause is excessive

elastase In molecular biology, elastase is an enzyme from the class of ''proteases (peptidases)'' that break down proteins. In particular, it is a serine protease. Forms and classification Eight human genes exist for elastase: Some bacteria (includin ...

release from

s and

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s. It has also been considered that mutations in elastin (ELN) and fibulin-5 (FBLN5) genes can increase susceptibility of elastic fibres to inflammatory degradation in acquired cutis laxa. Acquired cutis laxa has also been seen in conjunction with a number of conditions including:

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...

celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...

, and

monoclonal gammopathies Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, espe ...

. It can also occur as a postinflammatory response after

Urticarial Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

skin

fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...

s have shown a 2- to 3- fold increase in

activity in a patient with acquired cutis laxa.

Diagnosis

Treatment

As of 2019, there is no treatment for cutis laxa. Procedures aimed at mitigating symptoms and identifying subsequent conditions are often advised. No pharmacological agent has been able to stop the progression of the disease. However, cosmetic surgeries are potentially an option as cutis laxa does not generally involve vascular fragility.

References

External links

Medscape entry on Cutis Laxa
{{DEFAULTSORT:Cutis Laxa Abnormalities of dermal fibrous and elastic tissue Rare diseases