Paget’s Disease types Paget’s disease is not a single disorder but a confusing umbrella term used for three entirely unrelated conditions affecting bone, breast, and skin, each with distinct causes, mechanisms, and treatments. This is often a cause of confusion when the common man starts looking for information online, but the name Paget’s disease actually refers to three completely unrelated conditions. Not only are the conditions different, but they affect three separate organs, each with a different mechanism, and with completely different treatment options.
Why do they have the same name? They have been named after Sir James Paget, who described the bone condition in 1877 and the breast condition in 1874, so the name is historical. This causes genuine confusion in search results; someone googling “Paget’s disease” may have been told they have the bone type, the breast type, or the skin type and find information about the wrong one. In reality, these are all very distinct conditions.
Paget’s Disease of Bone: Paget’s Disease types
Paget’s disease of bone is a chronic disorder. It involves bone remodelling, wherein the normal cycle of old bone being broken down and new bone being built is disrupted. People of Western European descent seem to be more vulnerable. It’s not a disease very commonly known, and is rare in ages below 40, but it’s actually very common in older adults. Many people don’t know they have the disease, and it’s discovered incidentally when an X-ray is done for some other reason.
Pathophysiology
In healthy bone, osteoclasts break down the old bone and osteoblasts build new bone. This process is continuous and balanced, so the bone stays in shape. In Paget’s disease, these osteoclasts become overactive and start breaking down bone too fast. Osteoblasts try to compensate for this, but the new bone formed is disorganised, structurally weak, and enlarged.
As a result, the bones become bigger but are weaker than normal, and thus, are more prone to deformity, fractures, and pain. One thing to note is that Paget’s disease rarely affects the whole skeleton; most of the time, only one or a few bones are involved. It’s not restricted to a bone type either, and can affect any bone in the body, though some are more commonly affected: pelvis, spine, skull, femur (thigh bone), and tibia (shin bones).
The Disruption of Bone Remodeling in Paget’s Disease.(Left):In healthy bone, osteoclasts (purple) break down old bone while osteoblasts (blue) rebuild it in a precise, balanced cycle. The resulting bone matrix is strong and organized.(Right):In Paget’s disease,osteoclasts become overactive(giant cells), breaking down bone too rapidly. To compensate,osteoblasts build new bone haphazardly and in an unorganized way.This creates enlarged, structurally weak bones that are prone to deformity and fracture.
What Causes Paget’s Disease in the Bone
The exact cause of the disease isn’t known. It is believed to be a strong genetic component since up to 40% of cases have a family history. Mutations in the SQSTM1 gene are the most well-established genetic link.
The Three Radiological Phases of Paget’s Disease.(A) Lytic Phase:the earliest stage where overactive cells break down bone, creating distinct V-shaped or flame-like patterns in long bones. (B) Mixed Phase: A combination of bone destruction and disorganized repair, visible as significant thickening of the skull and pelvis. (C) Sclerotic Phase: The late stage, where bone becomes enlarged and structurally weak; classic ‘cotton wool’ patches in the skull.There is a loss of distinction between the core and outer shell in the tibia, leading to bowing and fractures. (Image Courtesy: Rendina, D., Falchetti, A., Diacinti, D. et al. Diagnosis and treatment of Paget’s disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS). J Endocrinol Invest 47, 1335–1360 (2024). Available fromSpringer Natureand licensed under CC by 4.0)
Some research also suggests that a slow-acting paramyxovirus infection (measles, canine distemper) may trigger Paget’s in genetically susceptible people. This is a debatable cause, though.
Environmental factors might also play a role, as the condition is becoming less common and less severe in some populations, probably as a result of some change in the environment.
The eventual trigger might be a combination of all three of these factors.
Symptoms of Paget’s Disease of Bone
Paget’s bone disease is asymptomatic in many people, which is why it remains underdiagnosed. When symptoms present, they might be:
- Deep bone pain,aching and persistent; worse at night. This is the most common presenting symptom
- Bone deformity, i.e, bowing of the legs, the skull becoming bigger (hat no longer fits), a curved spine
- Because of increased blood flow, the area over the affected bone may feel warmer
- The affected bones fracture more easily
- Neurological complications in cases where an enlarged bone of the skull or spine compresses nerves. It characteristically causes hearing loss and may also cause headaches, tingling, and weakness
- Rarely (<1%), osteosarcoma (bone cancer) can develop in the bone; in this case, pain suddenly becomes worse; this should be a warning sign
- Though it’s not a disease of the joint, if the bone near one is affected, it can cause secondary osteoarthritis to develop
Diagnosis of Paget’s Bone Disease
X-rays are how the disease is usually discovered, incidentally or when symptoms are suspected. The bones show characteristic changes: bone enlargement, coarsened trabecular pattern, and deformity.
Other imaging techniques can be a bone scan, CT, or MRI. A bone scan maps the entire skeleton so we can see which bones are affected. CT or MRI, on the other hand, are for assessing complications, specifically neurological ones. A classic finding is the ‘cotton wool’ appearance of the skull.
Among blood tests, an elevated ALP (alkaline phosphatase) is the hallmark finding. It reflects the rate of bone turnover, which is higher in Paget’s disease.
Whole-Body Bone Scan of Active Paget’s.A specialized tracer 99mTc-MDP highlights areas of high metabolic activity.Long Bones (A):characteristic bowing and intense activity along the length of the bone.Skeletal Districts (B & C):how the disease often affects an entire section of bone rather than just a small spot.The “Mickey Mouse” Sign (D):A classic diagnostic clue where the disease affects the spine, creating a distinctive three-pointed shape on the scan. These hot spots allow clinicians to map exactly which bones are involved before starting bisphosphonate treatment. (Image Courtesy: Rendina, D., Falchetti, A., Diacinti, D. et al. Diagnosis and treatment of Paget’s disease of bone: position paper from the Italian Society of Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS). J Endocrinol Invest 47, 1335–1360 (2024). Available fromSpringer Natureand licensed under CC by 4.0)
How is Paget’s Disease of The Bone Treated?
Treatment is actually not always needed, especially not if diagnosed early. In low-risk cases, the bones just need to be monitored. The goal is to relieve the pain, normalise ALP levels, and prevent complications; it’s not curable, it can only be managed.
- Bisphosphonates are the mainstay of treatment; they work by suppressing osteoclast activity so that the abnormal bone turnover slows down. They are usually given intravenously (via IV), but oral bisphosphonates might be given if IV is not appropriate.
- Zoledronic acid (a single IV infusion) is now the most common treatment option. It is incredibly effective; in fact, a single dose can induce remission lasting the next several years.
- Of course, if the disease has progressed much, like fractures or significant deformity, surgery might be needed. A joint replacement surgery might be needed if the patient develops secondary osteoarthritis.
- Over the course of treatment, ALP levels have to be checked periodically to keep track of progress and response to treatment.
- Calcium and vitamin D contribute to bone mineralization, so their supplementation is routinely recommended in patients.
The importance of prompt treatment cannot be overstated here; untreated Paget’s disease that is active and progressive can lead to permanent complications. If hearing loss results from skull involvement and nerve compression, it won’t reverse, and fractures in Pagetic bones also heal poorly. The window of opportunity where bisphosphonates can prevent these complications is before they develop, not after.
Paget’s Disease of the Breast
Unlike bone disease, this is a rare form of breast cancer. It affects the skin of the nipple and areola, and is significant in that it is almost always associated with an underlying cancer in the same breast. The cancer is either ductal carcinoma in situ (DCIS) orinvasive breast cancer.
It’s important to make this distinction that nipple changes are not the primary cancer; they are more of a sign that cancer cells have migrated from the tumor, along the milk ducts, to the surface of the skin.
Paget’s disease of the breast is an extremely rare cancer; it accounts for 1-4% of all breast cancers. Just like other breast cancers, it affects women predominantly but can also occur in men.
Symptoms of Paget’s Disease of the Breast
Symptoms of Paget’s disease are almost always unilateral. These symptoms can be:
- Eczema-like changes to the nipple: redness, scaly skin, crusting, flaking
- Itching or burning of the nipple
- Inverted or distorted nipple
- A lump may or may not be present
A dangerous pattern we see is that many women (and even some clinicians) treat it as eczema for several months before the correct diagnosis is made. In reality, eczema would affect both nipples and respond to steroids. On the other hand, Paget’s disease is unilateral and won’t respond to steroid creams.
Diagnosis of Paget’s Disease of the Breast
Because it mimics eczema for so long, the average delay in diagnosis for Paget’s disease of the breast can be as long as 6-12 months. Since it’s associated with breast cancer, the single most fatal cancer in women, any unilateral nipple skin change that doesn’t resolve within a few weeks needs a biopsy.
- The first diagnostic measure is a punch biopsy or surface scrape cytology of the nipple. It confirms the presence or absence of Paget cells (large, pale, malignant cells) under the microscope
- If Paget cells are identified, the next step is to identify the underlying tumor. Either a mammogram or a breast ultrasound can be done to find this out
- In some cases, the mammogram may not show a tumour, but the clinician still suspects something; in this case, an MRI of the breast is recommended.
Microscopic View of Paget Cells.Paget cells are large, pale cells with irregular nuclei that have invaded the skin’s surface (the epidermis). Unlike eczema, which is just inflammation, these cells represent a migration of malignancy. This proves that the skin change is a sign of an underlying condition rather than a simple allergy. (Image Courtesy: Giovannini, M., D’Atri, C., Piubello, Q.et al.Mammary Paget’s disease occurs after mastectomy.World J Surg Onc4, 51 (2006). Available fromSpringer Natureand licensed under CC by 4.0)
How is Paget’s Disease of the Breast Treated?
The treatment of choice in Paget’s breast disease is decided based on whether an underlying tumor is identified and what its extent is. A complete or partial mastectomy can be done depending on the extent of the tumour. Sometimes, surgery might not be necessary, and sometimes surgery might need to be supplemented with radiotherapy, chemotherapy, or hormone therapy.
The prognosis of Paget’s disease is generally good as long as it is diagnosed early, especially if DCIS is present and there is no invasive component.
Extramammary Paget’s Disease
Extramammary Paget’s disease is also not related at all to the bone condition, it’s the same type as Paget’s disease of the breast. The hallmark is the presence of malignant Paget cells in the skin, but occurring outside the breast. Instead, it affects areas like the vulva, perianal region, scrotum, axilla, or the penis. Vulvar cases are the most common, hence, it is more commonly known as vulvar Paget’s disease.
Like the breast type, it can be associated with an underlying cancer (colorectal, bladder, urological), but in a lot of cases, this is only a primary skin condition, and there is no underlying cancer. Overall, it is a rare condition, and predominantly affects older adults. Vulvar cases are most common in post-menopausal women.
Symptoms of Extramammary Paget’s Disease
The symptoms and subsequent misdiagnosis are similar to Paget’s disease of the breast:
- Chronic, persistent itching is the dominant symptom, often present for years before diagnosis
- Red, scaly, or white plaque on the affected skin
The delayed diagnosis pattern is consistent here as well; it is frequently misdiagnosed as eczema, psoriasis, or fungal infection. Thus, any chronic vulvar, perianal, or scrotal skin change that doesn’t respond to standard treatment like steroids needs a biopsy.
Extramammary Paget’s Disease (EMPD).Two reddish-brown, well-defined lesions on the chest(A)and the buttock(B). Because these lesions are located away from the typical sites and resemble common skin conditions like psoriasis or localized eczema, they are frequently misdiagnosed. This highlights the importance of a biopsy for any chronic, non-healing skin plaque, regardless of its location. (Image Courtesy: Yorita K, Hokimoto N, Sakamoto K, et al. (August 23, 2024) Simultaneous Occurrence of Two Ectopic Extramammary Paget Disease Lesions: A Case Report. Cureus 16(8): e67589. Available fromCureusand licensed under CC by 4.0)
Diagnosis and Treatment of Extramammary Paget’s Disease
Like Paget’s disease of the breast, a skin biopsy is the only way to confirm the diagnosis. If the biopsy shows Paget cells, the next step is to rule out an underlying malignancy; this can be via colonoscopy, cystoscopy, or imaging, depending on the location.
Treatment requires surgery, in the form of wide local excision, and yet, recurrence rates are high, even after clear margins. To reduce this, Mohs micrographic surgery is being used increasingly now. As an alternative to surgery, imiquimod cream is a form of topical immunotherapy that is used in some cases.
When To See a Doctor?
All three types of Paget’s disease are notorious for being diagnosed late; hence, there are some signs and symptoms that should prompt you to get suspicious and consult a doctor.
- Bones: Persistent bone pain, especially in older adults; unexplained hearing loss; a minor injury leading to a fracture; a noticeable increase in size of a finger bone or the skull
- Breast: Unilateral skin change of the nipple, can be scaling, crusting, redness, itching, that persists for several weeks and doesn’t respond to standard treatment like steroids
- Extramammary: Like the breast type, any chronic itching or skin change on the vulva, perianal area, or genitals that has not responded to standard treatment
Conclusion
If there is a common thread connecting the three types of Paget’s disease, it’s that delayed diagnosis is the biggest problem. The bone type often goes undiagnosed because it’s asymptomatic in many people. The breast and extramammary types in particular are both routinely mistaken for benign skin conditions. Sometimes, even after not showing any response to treatment, an accurate diagnosis isn’t made till months later, and the disease becomes worse.
References
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