Article

To the Editor:

An 82-year-old man presented to our dermatology clinic for a total-body skin examination due to a recently diagnosed primary melanoma of the left middle ear. He reported pain of the left ear and water behind the left eardrum of 1 year’s duration. An otorhinolaryngologist performed surgery due to the severe mastoiditis. A biopsy of the contents of the left middle ear revealed malignant melanoma. Positron emission tomography–computed tomography revealed the mass was mainly located in the anterior aspect of the left middle ear with suspicion of tumor extension into the bony portion of the eustachian tube. No other disease was present. Prior to presentation to dermatology, gross excision of the left middle ear with removal of additional melanoma was confirmed by biopsy, and further analysis revealed v-Raf murine sarcoma viral oncogene (BRAF) was not detected while cellular proto-oncogene receptor kinase (KIT) mutation was detected on exon 13p (K642E).

The patient had no family history of melanoma. He never smoked and did not have contact with hazardous material. Initial examination at our clinic revealed no other suspicious pigmented lesions. After additional negative workup by the oncologist, the patient was presented to the tumor board, and postoperative radiotherapy was recommended to improve local control. Eight months after the patient’s initial diagnosis of the primary middle ear melanoma, a computed tomography–guided right lung biopsy showed metastatic melanoma. After various treatment modalities were discussed with the patient and his family, he was started on pembrolizumab. After 6 months on pembrolizumab, the patient developed autoimmune pneumonitis and pembrolizumab was discontinued. The patient elected to discontinue treatment and died 6 months later.

Malignant melanoma with primary involvement of the middle ear and mastoid mucosa rarely has been reported.^1-3 Primary malignant melanoma of the middle ear mucosa is difficult to diagnose clinically. Difficulty and delay in diagnosis occur because of the location and frequent lack of pathognomonic symptoms of the disease.² A comprehensive literature review by Maxwell et al³ in 2018 of the 10 reported primary middle ear mucosal melanomas found that patients most commonly presented with otorrhea, aural fullness, and hearing loss. Less common symptoms included otalgia, tinnitus, and facial weakness. Clinical examination revealed patients presented with serous otitis and/or a visible mass within the middle ear or external auditory canal. These melanomas demonstrated particularly poor outcomes, with 70% mortality, 20% local recurrence, and 50% distant metastasis. Distant metastases that occurred with primary middle ear mucosal melanoma include lung, liver, intraparotid, abdomen, and cutaneous metastasis.³

The specific pathophysiologic factors underlying the development of primary malignant melanoma of the middle ear mucosa are not known.² The middle ear and its components develop from the first and second pharyngeal arches.⁴ Melanocyte precursors from the neural crest migrate during the seventh or eighth week of embryogenesis. These precursors migrate to the epidermis, various mucosal epithelial, hair follicles, dermis, retina, uveal tract, leptomeninges, inner ear, and other tissues.⁵ The ossicles of the middle ear develop from the neural crest⁶ and remain in the mesenchyme until the eighth month, when the surrounding tissue dissolves.⁴ Cutaneous melanomas arise from the malignant transformation of melanocytes in the skin of neural crest lineage. Noncutaneous melanomas are hypothesized to arise from melanoblasts migrating to noncutaneous organs after neural crest cells undergo an epithelial-mesenchymal translation.⁷

Melanoma 5-year survival rates vary based on the melanoma disease stage: 98% for stage 1, 90% for stage 2, 70% for stage 3, and 10% for stage 4. Although early-stage disease mainly is treated with surgery, advanced and unresectable disease is managed with different therapeutic options, including BRAF inhibitors such as vemurafenib, dabrafenib mesylate, and encorafenib; immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab; and oncolytic virus such as talimogene laherparepvec.^8,9

Ninety percent of melanomas are of cutaneous origin. Extracutaneous melanomas may be derived from the uvea, leptomeninges, mucous membranes, and gastrointestinal tract.¹⁰ Mucosal melanomas are rare and represent only approximately 1% of all melanomas.¹¹ In order of frequency, primary mucosal melanomas include the head and neck, anorectal region, vulvovaginal region, and urinary tract. UV radiation exposure is an important risk factor for cutaneous melanoma but has not been associated with the development of mucosal melanoma.⁷ In 2019, Altieri et al¹¹ analyzed 1824 cases of mucosal melanoma and found that anatomic site influences survival because mucosal melanomas in the most occult anatomic sites—spinal/central nervous system, lung and pleura, liver, and pancreas—have the worst prognosis, likely because they have already metastasized by the time they are diagnosed. Due to their occult anatomic location and lack of early presenting signs and symptoms, mucosal melanomas are difficult to diagnose at an early stage, resulting in a poorer prognosis compared with cutaneous melanomas. The most important prognostic indicator for cutaneous melanomas of tumor thickness (ie, Breslow depth) provides less prognostic value for patients with mucosal melanoma. Limitations also include the lack of a standardized staging system for mucosal melanoma, but Altieri et al¹¹ found that poorer survival in patients with mucosal melanoma was observed in relation to stage based on the clinical and pathologic tumor-node-metastasis staging system of the Surveillance, Epidemiology, and End Results program. An aggregate 5-year survival estimate of patients diagnosed with mucosal melanoma is 28%, underscoring that mucosal melanoma is an aggressive melanoma that carries a poor prognosis and warrants a more aggressive treatment approach at the time of diagnosis.¹¹

Common treatment of primary middle ear mucosal melanoma involves a multimodality therapy including surgical oncological resection for most patients. Currently, radiation is in use for adjuvant treatment and definitive therapy in unresectable tumors or patients who are poor surgical candidates. Malignant melanoma traditionally was considered radioresistant, yet considerable variability in responsiveness has been observed both within and between tumors. Although there are no defined indications for adjuvant therapy, it is often administered in advanced or recurrent cases and those with positive or close margins. Chemotherapy generally is reserved for patients with systemic disease. The chemotherapeutic agents that have been used in the treatment of patients with melanoma of the middle ear include the alkylating agents dacarbazine, cisplatin, nimustine, paclitaxel, and temozolomide. Also, chemotherapeutic agents that have been reported in the treatment of melanoma of the middle ear include tamoxifen, the selective estrogen receptor inhibitor, and interferon. Most recently, programed cell death protein 1 inhibitors pembrolizumab and nivolumab have been used in the treatment of middle ear melanoma. Outcomes remain poor with a high rate of mortality. Novel immunotherapeutic agents combined with adjuvant radiotherapy have been proposed to improve disease control and survival rates.³

Data on systemic therapies for mucosal melanomas are limited due to the rarity of the disease. Even with the development of novel therapies, outcomes remain poor for mucosal melanomas, and additional treatment strategies are needed. Although proto-oncogene BRAF mutations occur in 50% to 70% of cutaneous melanomas, these mutations are rare in mucosal melanomas.³ In mucosal melanomas, activating mutations of the cell receptor KIT are identified more frequently.⁷ Alterations in proto-oncogene KIT have been found in acral, mucosal, and cutaneous melanoma. KIT mutations were found on exons 11 and 13.¹² Variability in the biology of KIT is suggested. Treatment of melanomas with the KIT mutations with tyrosine inhibitors imatinib and nilotinib have shown variable benefits.¹⁰ In a 2019 study of 44 patients with mucosal melanoma, Moya-Plana et al¹³ found that in cases of unresectable and/or metastatic disease, immunotherapy with pembrolizumab had a better benefit-risk ratio than immune treatment with ipilimumab, a cytotoxic T-cell lymphocyte-associated protein 4 inhibitor.

Primary malignant melanoma of the middle ear is unusual and difficult to diagnose clinically. These melanomas have a poor prognosis and can have distant metastasis including cutaneous metastasis. We present this case to emphasize the need to be aware that melanoma can arise in the middle ear.

To the Editor:

An 82-year-old man presented to our dermatology clinic for a total-body skin examination due to a recently diagnosed primary melanoma of the left middle ear. He reported pain of the left ear and water behind the left eardrum of 1 year’s duration. An otorhinolaryngologist performed surgery due to the severe mastoiditis. A biopsy of the contents of the left middle ear revealed malignant melanoma. Positron emission tomography–computed tomography revealed the mass was mainly located in the anterior aspect of the left middle ear with suspicion of tumor extension into the bony portion of the eustachian tube. No other disease was present. Prior to presentation to dermatology, gross excision of the left middle ear with removal of additional melanoma was confirmed by biopsy, and further analysis revealed v-Raf murine sarcoma viral oncogene (BRAF) was not detected while cellular proto-oncogene receptor kinase (KIT) mutation was detected on exon 13p (K642E).

The patient had no family history of melanoma. He never smoked and did not have contact with hazardous material. Initial examination at our clinic revealed no other suspicious pigmented lesions. After additional negative workup by the oncologist, the patient was presented to the tumor board, and postoperative radiotherapy was recommended to improve local control. Eight months after the patient’s initial diagnosis of the primary middle ear melanoma, a computed tomography–guided right lung biopsy showed metastatic melanoma. After various treatment modalities were discussed with the patient and his family, he was started on pembrolizumab. After 6 months on pembrolizumab, the patient developed autoimmune pneumonitis and pembrolizumab was discontinued. The patient elected to discontinue treatment and died 6 months later.

Malignant melanoma with primary involvement of the middle ear and mastoid mucosa rarely has been reported.^1-3 Primary malignant melanoma of the middle ear mucosa is difficult to diagnose clinically. Difficulty and delay in diagnosis occur because of the location and frequent lack of pathognomonic symptoms of the disease.² A comprehensive literature review by Maxwell et al³ in 2018 of the 10 reported primary middle ear mucosal melanomas found that patients most commonly presented with otorrhea, aural fullness, and hearing loss. Less common symptoms included otalgia, tinnitus, and facial weakness. Clinical examination revealed patients presented with serous otitis and/or a visible mass within the middle ear or external auditory canal. These melanomas demonstrated particularly poor outcomes, with 70% mortality, 20% local recurrence, and 50% distant metastasis. Distant metastases that occurred with primary middle ear mucosal melanoma include lung, liver, intraparotid, abdomen, and cutaneous metastasis.³

The specific pathophysiologic factors underlying the development of primary malignant melanoma of the middle ear mucosa are not known.² The middle ear and its components develop from the first and second pharyngeal arches.⁴ Melanocyte precursors from the neural crest migrate during the seventh or eighth week of embryogenesis. These precursors migrate to the epidermis, various mucosal epithelial, hair follicles, dermis, retina, uveal tract, leptomeninges, inner ear, and other tissues.⁵ The ossicles of the middle ear develop from the neural crest⁶ and remain in the mesenchyme until the eighth month, when the surrounding tissue dissolves.⁴ Cutaneous melanomas arise from the malignant transformation of melanocytes in the skin of neural crest lineage. Noncutaneous melanomas are hypothesized to arise from melanoblasts migrating to noncutaneous organs after neural crest cells undergo an epithelial-mesenchymal translation.⁷

Melanoma 5-year survival rates vary based on the melanoma disease stage: 98% for stage 1, 90% for stage 2, 70% for stage 3, and 10% for stage 4. Although early-stage disease mainly is treated with surgery, advanced and unresectable disease is managed with different therapeutic options, including BRAF inhibitors such as vemurafenib, dabrafenib mesylate, and encorafenib; immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab; and oncolytic virus such as talimogene laherparepvec.^8,9

Ninety percent of melanomas are of cutaneous origin. Extracutaneous melanomas may be derived from the uvea, leptomeninges, mucous membranes, and gastrointestinal tract.¹⁰ Mucosal melanomas are rare and represent only approximately 1% of all melanomas.¹¹ In order of frequency, primary mucosal melanomas include the head and neck, anorectal region, vulvovaginal region, and urinary tract. UV radiation exposure is an important risk factor for cutaneous melanoma but has not been associated with the development of mucosal melanoma.⁷ In 2019, Altieri et al¹¹ analyzed 1824 cases of mucosal melanoma and found that anatomic site influences survival because mucosal melanomas in the most occult anatomic sites—spinal/central nervous system, lung and pleura, liver, and pancreas—have the worst prognosis, likely because they have already metastasized by the time they are diagnosed. Due to their occult anatomic location and lack of early presenting signs and symptoms, mucosal melanomas are difficult to diagnose at an early stage, resulting in a poorer prognosis compared with cutaneous melanomas. The most important prognostic indicator for cutaneous melanomas of tumor thickness (ie, Breslow depth) provides less prognostic value for patients with mucosal melanoma. Limitations also include the lack of a standardized staging system for mucosal melanoma, but Altieri et al¹¹ found that poorer survival in patients with mucosal melanoma was observed in relation to stage based on the clinical and pathologic tumor-node-metastasis staging system of the Surveillance, Epidemiology, and End Results program. An aggregate 5-year survival estimate of patients diagnosed with mucosal melanoma is 28%, underscoring that mucosal melanoma is an aggressive melanoma that carries a poor prognosis and warrants a more aggressive treatment approach at the time of diagnosis.¹¹

Common treatment of primary middle ear mucosal melanoma involves a multimodality therapy including surgical oncological resection for most patients. Currently, radiation is in use for adjuvant treatment and definitive therapy in unresectable tumors or patients who are poor surgical candidates. Malignant melanoma traditionally was considered radioresistant, yet considerable variability in responsiveness has been observed both within and between tumors. Although there are no defined indications for adjuvant therapy, it is often administered in advanced or recurrent cases and those with positive or close margins. Chemotherapy generally is reserved for patients with systemic disease. The chemotherapeutic agents that have been used in the treatment of patients with melanoma of the middle ear include the alkylating agents dacarbazine, cisplatin, nimustine, paclitaxel, and temozolomide. Also, chemotherapeutic agents that have been reported in the treatment of melanoma of the middle ear include tamoxifen, the selective estrogen receptor inhibitor, and interferon. Most recently, programed cell death protein 1 inhibitors pembrolizumab and nivolumab have been used in the treatment of middle ear melanoma. Outcomes remain poor with a high rate of mortality. Novel immunotherapeutic agents combined with adjuvant radiotherapy have been proposed to improve disease control and survival rates.³

Data on systemic therapies for mucosal melanomas are limited due to the rarity of the disease. Even with the development of novel therapies, outcomes remain poor for mucosal melanomas, and additional treatment strategies are needed. Although proto-oncogene BRAF mutations occur in 50% to 70% of cutaneous melanomas, these mutations are rare in mucosal melanomas.³ In mucosal melanomas, activating mutations of the cell receptor KIT are identified more frequently.⁷ Alterations in proto-oncogene KIT have been found in acral, mucosal, and cutaneous melanoma. KIT mutations were found on exons 11 and 13.¹² Variability in the biology of KIT is suggested. Treatment of melanomas with the KIT mutations with tyrosine inhibitors imatinib and nilotinib have shown variable benefits.¹⁰ In a 2019 study of 44 patients with mucosal melanoma, Moya-Plana et al¹³ found that in cases of unresectable and/or metastatic disease, immunotherapy with pembrolizumab had a better benefit-risk ratio than immune treatment with ipilimumab, a cytotoxic T-cell lymphocyte-associated protein 4 inhibitor.

Primary malignant melanoma of the middle ear is unusual and difficult to diagnose clinically. These melanomas have a poor prognosis and can have distant metastasis including cutaneous metastasis. We present this case to emphasize the need to be aware that melanoma can arise in the middle ear.

To the Editor:

An 82-year-old man presented to our dermatology clinic for a total-body skin examination due to a recently diagnosed primary melanoma of the left middle ear. He reported pain of the left ear and water behind the left eardrum of 1 year’s duration. An otorhinolaryngologist performed surgery due to the severe mastoiditis. A biopsy of the contents of the left middle ear revealed malignant melanoma. Positron emission tomography–computed tomography revealed the mass was mainly located in the anterior aspect of the left middle ear with suspicion of tumor extension into the bony portion of the eustachian tube. No other disease was present. Prior to presentation to dermatology, gross excision of the left middle ear with removal of additional melanoma was confirmed by biopsy, and further analysis revealed v-Raf murine sarcoma viral oncogene (BRAF) was not detected while cellular proto-oncogene receptor kinase (KIT) mutation was detected on exon 13p (K642E).

The patient had no family history of melanoma. He never smoked and did not have contact with hazardous material. Initial examination at our clinic revealed no other suspicious pigmented lesions. After additional negative workup by the oncologist, the patient was presented to the tumor board, and postoperative radiotherapy was recommended to improve local control. Eight months after the patient’s initial diagnosis of the primary middle ear melanoma, a computed tomography–guided right lung biopsy showed metastatic melanoma. After various treatment modalities were discussed with the patient and his family, he was started on pembrolizumab. After 6 months on pembrolizumab, the patient developed autoimmune pneumonitis and pembrolizumab was discontinued. The patient elected to discontinue treatment and died 6 months later.

Malignant melanoma with primary involvement of the middle ear and mastoid mucosa rarely has been reported.^1-3 Primary malignant melanoma of the middle ear mucosa is difficult to diagnose clinically. Difficulty and delay in diagnosis occur because of the location and frequent lack of pathognomonic symptoms of the disease.² A comprehensive literature review by Maxwell et al³ in 2018 of the 10 reported primary middle ear mucosal melanomas found that patients most commonly presented with otorrhea, aural fullness, and hearing loss. Less common symptoms included otalgia, tinnitus, and facial weakness. Clinical examination revealed patients presented with serous otitis and/or a visible mass within the middle ear or external auditory canal. These melanomas demonstrated particularly poor outcomes, with 70% mortality, 20% local recurrence, and 50% distant metastasis. Distant metastases that occurred with primary middle ear mucosal melanoma include lung, liver, intraparotid, abdomen, and cutaneous metastasis.³

The specific pathophysiologic factors underlying the development of primary malignant melanoma of the middle ear mucosa are not known.² The middle ear and its components develop from the first and second pharyngeal arches.⁴ Melanocyte precursors from the neural crest migrate during the seventh or eighth week of embryogenesis. These precursors migrate to the epidermis, various mucosal epithelial, hair follicles, dermis, retina, uveal tract, leptomeninges, inner ear, and other tissues.⁵ The ossicles of the middle ear develop from the neural crest⁶ and remain in the mesenchyme until the eighth month, when the surrounding tissue dissolves.⁴ Cutaneous melanomas arise from the malignant transformation of melanocytes in the skin of neural crest lineage. Noncutaneous melanomas are hypothesized to arise from melanoblasts migrating to noncutaneous organs after neural crest cells undergo an epithelial-mesenchymal translation.⁷

Melanoma 5-year survival rates vary based on the melanoma disease stage: 98% for stage 1, 90% for stage 2, 70% for stage 3, and 10% for stage 4. Although early-stage disease mainly is treated with surgery, advanced and unresectable disease is managed with different therapeutic options, including BRAF inhibitors such as vemurafenib, dabrafenib mesylate, and encorafenib; immune checkpoint inhibitors such as ipilimumab, nivolumab, and pembrolizumab; and oncolytic virus such as talimogene laherparepvec.^8,9

Ninety percent of melanomas are of cutaneous origin. Extracutaneous melanomas may be derived from the uvea, leptomeninges, mucous membranes, and gastrointestinal tract.¹⁰ Mucosal melanomas are rare and represent only approximately 1% of all melanomas.¹¹ In order of frequency, primary mucosal melanomas include the head and neck, anorectal region, vulvovaginal region, and urinary tract. UV radiation exposure is an important risk factor for cutaneous melanoma but has not been associated with the development of mucosal melanoma.⁷ In 2019, Altieri et al¹¹ analyzed 1824 cases of mucosal melanoma and found that anatomic site influences survival because mucosal melanomas in the most occult anatomic sites—spinal/central nervous system, lung and pleura, liver, and pancreas—have the worst prognosis, likely because they have already metastasized by the time they are diagnosed. Due to their occult anatomic location and lack of early presenting signs and symptoms, mucosal melanomas are difficult to diagnose at an early stage, resulting in a poorer prognosis compared with cutaneous melanomas. The most important prognostic indicator for cutaneous melanomas of tumor thickness (ie, Breslow depth) provides less prognostic value for patients with mucosal melanoma. Limitations also include the lack of a standardized staging system for mucosal melanoma, but Altieri et al¹¹ found that poorer survival in patients with mucosal melanoma was observed in relation to stage based on the clinical and pathologic tumor-node-metastasis staging system of the Surveillance, Epidemiology, and End Results program. An aggregate 5-year survival estimate of patients diagnosed with mucosal melanoma is 28%, underscoring that mucosal melanoma is an aggressive melanoma that carries a poor prognosis and warrants a more aggressive treatment approach at the time of diagnosis.¹¹

Common treatment of primary middle ear mucosal melanoma involves a multimodality therapy including surgical oncological resection for most patients. Currently, radiation is in use for adjuvant treatment and definitive therapy in unresectable tumors or patients who are poor surgical candidates. Malignant melanoma traditionally was considered radioresistant, yet considerable variability in responsiveness has been observed both within and between tumors. Although there are no defined indications for adjuvant therapy, it is often administered in advanced or recurrent cases and those with positive or close margins. Chemotherapy generally is reserved for patients with systemic disease. The chemotherapeutic agents that have been used in the treatment of patients with melanoma of the middle ear include the alkylating agents dacarbazine, cisplatin, nimustine, paclitaxel, and temozolomide. Also, chemotherapeutic agents that have been reported in the treatment of melanoma of the middle ear include tamoxifen, the selective estrogen receptor inhibitor, and interferon. Most recently, programed cell death protein 1 inhibitors pembrolizumab and nivolumab have been used in the treatment of middle ear melanoma. Outcomes remain poor with a high rate of mortality. Novel immunotherapeutic agents combined with adjuvant radiotherapy have been proposed to improve disease control and survival rates.³

Data on systemic therapies for mucosal melanomas are limited due to the rarity of the disease. Even with the development of novel therapies, outcomes remain poor for mucosal melanomas, and additional treatment strategies are needed. Although proto-oncogene BRAF mutations occur in 50% to 70% of cutaneous melanomas, these mutations are rare in mucosal melanomas.³ In mucosal melanomas, activating mutations of the cell receptor KIT are identified more frequently.⁷ Alterations in proto-oncogene KIT have been found in acral, mucosal, and cutaneous melanoma. KIT mutations were found on exons 11 and 13.¹² Variability in the biology of KIT is suggested. Treatment of melanomas with the KIT mutations with tyrosine inhibitors imatinib and nilotinib have shown variable benefits.¹⁰ In a 2019 study of 44 patients with mucosal melanoma, Moya-Plana et al¹³ found that in cases of unresectable and/or metastatic disease, immunotherapy with pembrolizumab had a better benefit-risk ratio than immune treatment with ipilimumab, a cytotoxic T-cell lymphocyte-associated protein 4 inhibitor.

Primary malignant melanoma of the middle ear is unusual and difficult to diagnose clinically. These melanomas have a poor prognosis and can have distant metastasis including cutaneous metastasis. We present this case to emphasize the need to be aware that melanoma can arise in the middle ear.

To the Editor:

The posttraumatic pseudolipoma (PTL) is a painless localized mass comprised of unencapsulated adipose tissue that develops at the site of acute or prolonged blunt soft tissue trauma. It may be round or fusiform in shape and has areas of saponification leading to fat necrosis.¹ Posttraumatic pseudolipomas are 12 times more likely to occur in females, which may be attributed to sex-determined adipose tissue distribution or cosmetic concerns.² Most PTLs are found in areas of the body with high adiposity, including the hip, thigh, and gluteal regions.³ A patient history of a traumatic event resulting in a hematoma and a subsequent latent period of several months to years before the pseudolipoma formation occurs is common.^1,2,4-6

A 27-year-old woman presented to the family medicine clinic for examination of a deformity on the right buttock. She noticed a soft protruding mass months after landing on the buttocks and on top of a stick during routine physical training. Prior ultrasonography of the deformity proved unhelpful in determining the etiology. Physical examination revealed a protruding, 2-cm, flesh-colored mass on the right buttock intergluteal fold that was soft, compressible, and nontender (Figure 1). There was no capsule, nodule, loculation, or sinus tract. The patient underwent excisional resection with findings of benign-appearing unencapsulated adipose tissue (Figure 2). The wound was closed without difficulty. After several weeks, she had a well-healing scar without contour deficits of the buttocks. Two to 3 months after the initial repair, the patient presented to the family medicine clinic with recurrence of the fatty protrusion. She was referred for consultation and definitive management to a plastic surgeon but was lost to follow up.

In a systematic review of the literature to research pathogenesis theories, a PubMed search of articles indexed for MEDLINE using the terms trauma and pseudolipoma, lipoma, fat, or adipose yielded 45 citations, with only 10 publications addressing the pathology specific to pseudolipomas. Two leading theories of the pathogenesis of PTLs include the adipose herniation pathway and the inflammatory proliferation pathway.^4,5

Adipose tissue comprises fat lobules that are organized underneath the supportive elastic fascial layers. Injury from forces exceeding the fascial strength is the basis for the oldest pathogenesis theory. The adipose herniation theory suggests that fat lobules are displaced through the damaged septae, allowing for the development of an epidermal pseudolipoma at the site of blunt trauma.⁷ This theory has been supported by many case reports; however, more recent reports have identified a larger number of PTL cases that showed no identifiable disruptions in the fascia.^1,4,8

In 1997, the inflammatory proliferation theory began to gain attention. The theory describes how local tissue trauma leads to the release of inflammatory cytokines, which successively signals the development of preadipocytes or adipose tissue–derived stem cells (ASCs) into mature adipocytes.⁴ Most patients report a history of a hematoma in the area of pseudolipoma development, which strongly supports this newer theory. Studies exploring hematomas have found elevated levels of growth factors and inflammatory markers.^2,9 In particular, tumor necrosis factor α, peroxisome proliferator–activated receptor γ, vascular endothelial growth factor, and IL-6 and IL-8 may foster an environment in which adipogenic cells are both chemotaxed to the area of trauma and differentiated to white adipose tissue.^2,10

Despite addressing the role of the preadipocyte, the available research fails to address the general development of mesenchymal cells into the preadipocyte. White adipose tissue develops at sites of neovascularization and frequently has been observed spreading into the nearby tissue toward other blood vessels. Furthermore, these white adipose tissue expansions remain reliant on multiple growth factors and cell-signaling molecules.¹⁰ Numerous investigations into stem cell grafting have found that implantation of ASCs in vivo within animal models does not result in the proliferation and differentiation of ASCs unless specific conditions have been met such as prior tissue injury or immunodeficiency.^10-12 These investigations support and expand on the inflammatory proliferation pathway. Thus, most of the true PTLs in the available research appear as de novo tumors and are more congruent with the inflammatory proliferation model.^1,2,4-6,8

Typical treatment of a PTL is surgical excision or liposuction depending on the pathology and size of the pseudolipoma. Biopsy examination prior to liposuction is critical for evaluation of liposarcoma and may help identify damage to Scarpa fascia. Recurrence of a PTL is rare regardless of treatment method; however, in a study of 31 PTL cases, only 6 were pathologically identified as PTLs without fibrous material.¹

Our patient experienced a blunt trauma to the buttocks and subsequently developed a PTL that was surgically excised and recurred within 3 months. Research surrounding the pathogenesis of the PTL has evolved from the theory of physical herniation of adipose tissue to an inflammatory differentiation of preadipocytes, but there is still much to learn about how and why it occurs and the mesenchymal differentiation following tissue injury.

To the Editor:

The posttraumatic pseudolipoma (PTL) is a painless localized mass comprised of unencapsulated adipose tissue that develops at the site of acute or prolonged blunt soft tissue trauma. It may be round or fusiform in shape and has areas of saponification leading to fat necrosis.¹ Posttraumatic pseudolipomas are 12 times more likely to occur in females, which may be attributed to sex-determined adipose tissue distribution or cosmetic concerns.² Most PTLs are found in areas of the body with high adiposity, including the hip, thigh, and gluteal regions.³ A patient history of a traumatic event resulting in a hematoma and a subsequent latent period of several months to years before the pseudolipoma formation occurs is common.^1,2,4-6

A 27-year-old woman presented to the family medicine clinic for examination of a deformity on the right buttock. She noticed a soft protruding mass months after landing on the buttocks and on top of a stick during routine physical training. Prior ultrasonography of the deformity proved unhelpful in determining the etiology. Physical examination revealed a protruding, 2-cm, flesh-colored mass on the right buttock intergluteal fold that was soft, compressible, and nontender (Figure 1). There was no capsule, nodule, loculation, or sinus tract. The patient underwent excisional resection with findings of benign-appearing unencapsulated adipose tissue (Figure 2). The wound was closed without difficulty. After several weeks, she had a well-healing scar without contour deficits of the buttocks. Two to 3 months after the initial repair, the patient presented to the family medicine clinic with recurrence of the fatty protrusion. She was referred for consultation and definitive management to a plastic surgeon but was lost to follow up.

In a systematic review of the literature to research pathogenesis theories, a PubMed search of articles indexed for MEDLINE using the terms trauma and pseudolipoma, lipoma, fat, or adipose yielded 45 citations, with only 10 publications addressing the pathology specific to pseudolipomas. Two leading theories of the pathogenesis of PTLs include the adipose herniation pathway and the inflammatory proliferation pathway.^4,5

Adipose tissue comprises fat lobules that are organized underneath the supportive elastic fascial layers. Injury from forces exceeding the fascial strength is the basis for the oldest pathogenesis theory. The adipose herniation theory suggests that fat lobules are displaced through the damaged septae, allowing for the development of an epidermal pseudolipoma at the site of blunt trauma.⁷ This theory has been supported by many case reports; however, more recent reports have identified a larger number of PTL cases that showed no identifiable disruptions in the fascia.^1,4,8

In 1997, the inflammatory proliferation theory began to gain attention. The theory describes how local tissue trauma leads to the release of inflammatory cytokines, which successively signals the development of preadipocytes or adipose tissue–derived stem cells (ASCs) into mature adipocytes.⁴ Most patients report a history of a hematoma in the area of pseudolipoma development, which strongly supports this newer theory. Studies exploring hematomas have found elevated levels of growth factors and inflammatory markers.^2,9 In particular, tumor necrosis factor α, peroxisome proliferator–activated receptor γ, vascular endothelial growth factor, and IL-6 and IL-8 may foster an environment in which adipogenic cells are both chemotaxed to the area of trauma and differentiated to white adipose tissue.^2,10

Despite addressing the role of the preadipocyte, the available research fails to address the general development of mesenchymal cells into the preadipocyte. White adipose tissue develops at sites of neovascularization and frequently has been observed spreading into the nearby tissue toward other blood vessels. Furthermore, these white adipose tissue expansions remain reliant on multiple growth factors and cell-signaling molecules.¹⁰ Numerous investigations into stem cell grafting have found that implantation of ASCs in vivo within animal models does not result in the proliferation and differentiation of ASCs unless specific conditions have been met such as prior tissue injury or immunodeficiency.^10-12 These investigations support and expand on the inflammatory proliferation pathway. Thus, most of the true PTLs in the available research appear as de novo tumors and are more congruent with the inflammatory proliferation model.^1,2,4-6,8

Typical treatment of a PTL is surgical excision or liposuction depending on the pathology and size of the pseudolipoma. Biopsy examination prior to liposuction is critical for evaluation of liposarcoma and may help identify damage to Scarpa fascia. Recurrence of a PTL is rare regardless of treatment method; however, in a study of 31 PTL cases, only 6 were pathologically identified as PTLs without fibrous material.¹

Our patient experienced a blunt trauma to the buttocks and subsequently developed a PTL that was surgically excised and recurred within 3 months. Research surrounding the pathogenesis of the PTL has evolved from the theory of physical herniation of adipose tissue to an inflammatory differentiation of preadipocytes, but there is still much to learn about how and why it occurs and the mesenchymal differentiation following tissue injury.

To the Editor:

The posttraumatic pseudolipoma (PTL) is a painless localized mass comprised of unencapsulated adipose tissue that develops at the site of acute or prolonged blunt soft tissue trauma. It may be round or fusiform in shape and has areas of saponification leading to fat necrosis.¹ Posttraumatic pseudolipomas are 12 times more likely to occur in females, which may be attributed to sex-determined adipose tissue distribution or cosmetic concerns.² Most PTLs are found in areas of the body with high adiposity, including the hip, thigh, and gluteal regions.³ A patient history of a traumatic event resulting in a hematoma and a subsequent latent period of several months to years before the pseudolipoma formation occurs is common.^1,2,4-6

A 27-year-old woman presented to the family medicine clinic for examination of a deformity on the right buttock. She noticed a soft protruding mass months after landing on the buttocks and on top of a stick during routine physical training. Prior ultrasonography of the deformity proved unhelpful in determining the etiology. Physical examination revealed a protruding, 2-cm, flesh-colored mass on the right buttock intergluteal fold that was soft, compressible, and nontender (Figure 1). There was no capsule, nodule, loculation, or sinus tract. The patient underwent excisional resection with findings of benign-appearing unencapsulated adipose tissue (Figure 2). The wound was closed without difficulty. After several weeks, she had a well-healing scar without contour deficits of the buttocks. Two to 3 months after the initial repair, the patient presented to the family medicine clinic with recurrence of the fatty protrusion. She was referred for consultation and definitive management to a plastic surgeon but was lost to follow up.

In a systematic review of the literature to research pathogenesis theories, a PubMed search of articles indexed for MEDLINE using the terms trauma and pseudolipoma, lipoma, fat, or adipose yielded 45 citations, with only 10 publications addressing the pathology specific to pseudolipomas. Two leading theories of the pathogenesis of PTLs include the adipose herniation pathway and the inflammatory proliferation pathway.^4,5

Adipose tissue comprises fat lobules that are organized underneath the supportive elastic fascial layers. Injury from forces exceeding the fascial strength is the basis for the oldest pathogenesis theory. The adipose herniation theory suggests that fat lobules are displaced through the damaged septae, allowing for the development of an epidermal pseudolipoma at the site of blunt trauma.⁷ This theory has been supported by many case reports; however, more recent reports have identified a larger number of PTL cases that showed no identifiable disruptions in the fascia.^1,4,8

In 1997, the inflammatory proliferation theory began to gain attention. The theory describes how local tissue trauma leads to the release of inflammatory cytokines, which successively signals the development of preadipocytes or adipose tissue–derived stem cells (ASCs) into mature adipocytes.⁴ Most patients report a history of a hematoma in the area of pseudolipoma development, which strongly supports this newer theory. Studies exploring hematomas have found elevated levels of growth factors and inflammatory markers.^2,9 In particular, tumor necrosis factor α, peroxisome proliferator–activated receptor γ, vascular endothelial growth factor, and IL-6 and IL-8 may foster an environment in which adipogenic cells are both chemotaxed to the area of trauma and differentiated to white adipose tissue.^2,10

Despite addressing the role of the preadipocyte, the available research fails to address the general development of mesenchymal cells into the preadipocyte. White adipose tissue develops at sites of neovascularization and frequently has been observed spreading into the nearby tissue toward other blood vessels. Furthermore, these white adipose tissue expansions remain reliant on multiple growth factors and cell-signaling molecules.¹⁰ Numerous investigations into stem cell grafting have found that implantation of ASCs in vivo within animal models does not result in the proliferation and differentiation of ASCs unless specific conditions have been met such as prior tissue injury or immunodeficiency.^10-12 These investigations support and expand on the inflammatory proliferation pathway. Thus, most of the true PTLs in the available research appear as de novo tumors and are more congruent with the inflammatory proliferation model.^1,2,4-6,8

Typical treatment of a PTL is surgical excision or liposuction depending on the pathology and size of the pseudolipoma. Biopsy examination prior to liposuction is critical for evaluation of liposarcoma and may help identify damage to Scarpa fascia. Recurrence of a PTL is rare regardless of treatment method; however, in a study of 31 PTL cases, only 6 were pathologically identified as PTLs without fibrous material.¹

Our patient experienced a blunt trauma to the buttocks and subsequently developed a PTL that was surgically excised and recurred within 3 months. Research surrounding the pathogenesis of the PTL has evolved from the theory of physical herniation of adipose tissue to an inflammatory differentiation of preadipocytes, but there is still much to learn about how and why it occurs and the mesenchymal differentiation following tissue injury.

Key clinical point: Overall, COVID-19 vaccines were well tolerated in patients with rheumatoid arthritis (RA), with the adverse event (AE) profile being comparable to that in control individuals; patients receiving methotrexate and hydroxychloroquine vs other immunosuppressants reporting fewer minor AE.

Major finding: At 7 days after vaccination, 76.9% of patients with RA reported AE, all being minor and comparable to those in the control group and similar between patients with active and inactive disease. Major AE were reported by 4.2% of patients with RA. Patients receiving methotrexate or hydroxychloroquine vs other immunosuppressants reported fewer minor AE (all P ≤ .05).

Study details: This was a cross-sectional survey-based study of 9462 respondents of an online self-reported questionnaire, including patients with RA (n = 1347), other autoimmune rheumatic diseases (n = 2305), non-rheumatic autoimmune diseases (n = 1079), and the control group (n = 4741) who received at least one dose of any COVID-19 vaccine.

Disclosures: This study did not receive any specific funding. Several authors reported receiving advisory board or speaker honoraria, consulting fees, research grant, or funding from various sources.

Source: Naveen R et al. COVID-19 vaccination in autoimmune diseases (COVAD) Study: Vaccine safety and tolerance in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Oct 31). Doi: 10.1093/rheumatology/keac624

Key clinical point: Overall, COVID-19 vaccines were well tolerated in patients with rheumatoid arthritis (RA), with the adverse event (AE) profile being comparable to that in control individuals; patients receiving methotrexate and hydroxychloroquine vs other immunosuppressants reporting fewer minor AE.

Major finding: At 7 days after vaccination, 76.9% of patients with RA reported AE, all being minor and comparable to those in the control group and similar between patients with active and inactive disease. Major AE were reported by 4.2% of patients with RA. Patients receiving methotrexate or hydroxychloroquine vs other immunosuppressants reported fewer minor AE (all P ≤ .05).

Study details: This was a cross-sectional survey-based study of 9462 respondents of an online self-reported questionnaire, including patients with RA (n = 1347), other autoimmune rheumatic diseases (n = 2305), non-rheumatic autoimmune diseases (n = 1079), and the control group (n = 4741) who received at least one dose of any COVID-19 vaccine.

Disclosures: This study did not receive any specific funding. Several authors reported receiving advisory board or speaker honoraria, consulting fees, research grant, or funding from various sources.

Source: Naveen R et al. COVID-19 vaccination in autoimmune diseases (COVAD) Study: Vaccine safety and tolerance in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Oct 31). Doi: 10.1093/rheumatology/keac624

Key clinical point: Overall, COVID-19 vaccines were well tolerated in patients with rheumatoid arthritis (RA), with the adverse event (AE) profile being comparable to that in control individuals; patients receiving methotrexate and hydroxychloroquine vs other immunosuppressants reporting fewer minor AE.

Major finding: At 7 days after vaccination, 76.9% of patients with RA reported AE, all being minor and comparable to those in the control group and similar between patients with active and inactive disease. Major AE were reported by 4.2% of patients with RA. Patients receiving methotrexate or hydroxychloroquine vs other immunosuppressants reported fewer minor AE (all P ≤ .05).

Study details: This was a cross-sectional survey-based study of 9462 respondents of an online self-reported questionnaire, including patients with RA (n = 1347), other autoimmune rheumatic diseases (n = 2305), non-rheumatic autoimmune diseases (n = 1079), and the control group (n = 4741) who received at least one dose of any COVID-19 vaccine.

Disclosures: This study did not receive any specific funding. Several authors reported receiving advisory board or speaker honoraria, consulting fees, research grant, or funding from various sources.

Source: Naveen R et al. COVID-19 vaccination in autoimmune diseases (COVAD) Study: Vaccine safety and tolerance in rheumatoid arthritis. Rheumatology (Oxford). 2022 (Oct 31). Doi: 10.1093/rheumatology/keac624

Key clinical point: Filgotinib vs placebo, both with background methotrexate, significantly improved disease activity and suppressed radiographic progression in patients with rheumatoid arthritis (RA) who were methotrexate inadequate responders (IR) and had ≤4 poor prognostic factors (PPF).

Major finding: Doses of 100 and 200 mg filgotinib vs placebo led to higher American College of Rheumatology 20, 50, and 70 response rates among patients with ≤4 PPF at week 12 (all P < .05) and significantly reduced the change from baseline in modified total Sharp score at week 24 among patients with 4 PPF (both P < .01) along with similar tolerability.

Study details: This post hoc analysis of FINCH 1 included 1755 patients with RA who were methotrexate-IR and were randomly assigned to receive filgotinib, adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by Gilead Sciences, Inc., with support from Eisai Co., Ltd., and Gilead Sciences K.K. Seven authors declared being current or former employees of Gilead Sciences/Galapagos BV or shareholders of various sources. Several authors reported ties with various sources.

Source: Combe BG et al. Efficacy and safety of filgotinib in patients with high risk of poor prognosis who showed inadequate response to MTX: A post hoc analysis of the FINCH 1 study. Rheumatol Ther. 2022 (Oct 9). Doi: 10.1007/s40744-022-00498-x

Key clinical point: Filgotinib vs placebo, both with background methotrexate, significantly improved disease activity and suppressed radiographic progression in patients with rheumatoid arthritis (RA) who were methotrexate inadequate responders (IR) and had ≤4 poor prognostic factors (PPF).

Major finding: Doses of 100 and 200 mg filgotinib vs placebo led to higher American College of Rheumatology 20, 50, and 70 response rates among patients with ≤4 PPF at week 12 (all P < .05) and significantly reduced the change from baseline in modified total Sharp score at week 24 among patients with 4 PPF (both P < .01) along with similar tolerability.

Study details: This post hoc analysis of FINCH 1 included 1755 patients with RA who were methotrexate-IR and were randomly assigned to receive filgotinib, adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by Gilead Sciences, Inc., with support from Eisai Co., Ltd., and Gilead Sciences K.K. Seven authors declared being current or former employees of Gilead Sciences/Galapagos BV or shareholders of various sources. Several authors reported ties with various sources.

Source: Combe BG et al. Efficacy and safety of filgotinib in patients with high risk of poor prognosis who showed inadequate response to MTX: A post hoc analysis of the FINCH 1 study. Rheumatol Ther. 2022 (Oct 9). Doi: 10.1007/s40744-022-00498-x

Key clinical point: Filgotinib vs placebo, both with background methotrexate, significantly improved disease activity and suppressed radiographic progression in patients with rheumatoid arthritis (RA) who were methotrexate inadequate responders (IR) and had ≤4 poor prognostic factors (PPF).

Major finding: Doses of 100 and 200 mg filgotinib vs placebo led to higher American College of Rheumatology 20, 50, and 70 response rates among patients with ≤4 PPF at week 12 (all P < .05) and significantly reduced the change from baseline in modified total Sharp score at week 24 among patients with 4 PPF (both P < .01) along with similar tolerability.

Study details: This post hoc analysis of FINCH 1 included 1755 patients with RA who were methotrexate-IR and were randomly assigned to receive filgotinib, adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by Gilead Sciences, Inc., with support from Eisai Co., Ltd., and Gilead Sciences K.K. Seven authors declared being current or former employees of Gilead Sciences/Galapagos BV or shareholders of various sources. Several authors reported ties with various sources.

Source: Combe BG et al. Efficacy and safety of filgotinib in patients with high risk of poor prognosis who showed inadequate response to MTX: A post hoc analysis of the FINCH 1 study. Rheumatol Ther. 2022 (Oct 9). Doi: 10.1007/s40744-022-00498-x

Key clinical point: Presence of autoantibodies for cyclic citrullinated peptide (anti-CCP2), load of anticitrullinated protein antibody (ACPA) fine-specificities, and immunoglobulin M (IgM) rheumatoid factor (RF) at diagnosis of rheumatoid arthritis (RA) increased the risk for incident venous thromboembolic events (VTE) in patients with RA.

Major finding: Positivity for IgG anti-CCP2 (hazard ratio [HR] 1.33; 95% CI 1.00-1.78) and IgM RF (HR 1.38; 95% CI 1.04-1.83) increased the risk for incident VTE. Additionally, the risk increased with the number of ACPA fine-specificities expressed (P_trend = .033).

Study details: This prospective cohort study analyzed 2782 patients with newly diagnosed RA who reported 213 first-ever VTE.

Disclosures: This study was supported by the Swedish Research Council, NordForsk, and others. Four authors declared being employees or part-time employees, paid advisors, or founders of different companies. Two authors reported owning patents for peptides and their use for diagnostic purpose.

Source: Westerlind H et al. The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Oct 18). Doi: 10.1093/rheumatology/keac601

Key clinical point: Presence of autoantibodies for cyclic citrullinated peptide (anti-CCP2), load of anticitrullinated protein antibody (ACPA) fine-specificities, and immunoglobulin M (IgM) rheumatoid factor (RF) at diagnosis of rheumatoid arthritis (RA) increased the risk for incident venous thromboembolic events (VTE) in patients with RA.

Major finding: Positivity for IgG anti-CCP2 (hazard ratio [HR] 1.33; 95% CI 1.00-1.78) and IgM RF (HR 1.38; 95% CI 1.04-1.83) increased the risk for incident VTE. Additionally, the risk increased with the number of ACPA fine-specificities expressed (P_trend = .033).

Study details: This prospective cohort study analyzed 2782 patients with newly diagnosed RA who reported 213 first-ever VTE.

Disclosures: This study was supported by the Swedish Research Council, NordForsk, and others. Four authors declared being employees or part-time employees, paid advisors, or founders of different companies. Two authors reported owning patents for peptides and their use for diagnostic purpose.

Source: Westerlind H et al. The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Oct 18). Doi: 10.1093/rheumatology/keac601

Key clinical point: Presence of autoantibodies for cyclic citrullinated peptide (anti-CCP2), load of anticitrullinated protein antibody (ACPA) fine-specificities, and immunoglobulin M (IgM) rheumatoid factor (RF) at diagnosis of rheumatoid arthritis (RA) increased the risk for incident venous thromboembolic events (VTE) in patients with RA.

Major finding: Positivity for IgG anti-CCP2 (hazard ratio [HR] 1.33; 95% CI 1.00-1.78) and IgM RF (HR 1.38; 95% CI 1.04-1.83) increased the risk for incident VTE. Additionally, the risk increased with the number of ACPA fine-specificities expressed (P_trend = .033).

Study details: This prospective cohort study analyzed 2782 patients with newly diagnosed RA who reported 213 first-ever VTE.

Disclosures: This study was supported by the Swedish Research Council, NordForsk, and others. Four authors declared being employees or part-time employees, paid advisors, or founders of different companies. Two authors reported owning patents for peptides and their use for diagnostic purpose.

Source: Westerlind H et al. The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis. Rheumatology (Oxford). 2022 (Oct 18). Doi: 10.1093/rheumatology/keac601

Key clinical point: Concomitant methotrexate significantly reduced humoral response to the third SARS-CoV-2 mRNA vaccine in older (age ≥ 64.5 years) but not younger (age < 64.5 years) patients with rheumatoid arthritis (RA).

Major finding: Patients aged ≥ 64.5 years receiving methotrexate plus biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) vs methotrexate monotherapy or b/tsDMARD monotherapy had significantly lower serum levels of immunoglobulin G antibody for SARS-CoV-2 spike protein receptor binding domain (64.8 vs 1743.8 or 1106.0 binding antibody units/mL, respectively; Kruskal-Wallis Test, P < .001), whereas patients aged < 64.5 years showed no significant difference (Kruskal-Wallis Test, P = .334).

Study details: Findings are from a retrospective analysis including 136 patients with RA treated with conventional synthetic DMARD or b/ts DMARD with or without methotrexate who received the third dose of SARS-CoV-2 mRNA vaccines BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna).

Disclosures: This study did not declare any specific source of funding. No conflict of interests was declared.

Source: Stahl D et al. Reduced humoral response to a third dose (booster) of SARS-CoV-2 mRNA vaccines by concomitant methotrexate therapy in elderly patients with rheumatoid arthritis. RMD Open. 2022;8(2):e002632 (Oct 10). Doi: 10.1136/rmdopen-2022-002632

Key clinical point: Concomitant methotrexate significantly reduced humoral response to the third SARS-CoV-2 mRNA vaccine in older (age ≥ 64.5 years) but not younger (age < 64.5 years) patients with rheumatoid arthritis (RA).

Major finding: Patients aged ≥ 64.5 years receiving methotrexate plus biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) vs methotrexate monotherapy or b/tsDMARD monotherapy had significantly lower serum levels of immunoglobulin G antibody for SARS-CoV-2 spike protein receptor binding domain (64.8 vs 1743.8 or 1106.0 binding antibody units/mL, respectively; Kruskal-Wallis Test, P < .001), whereas patients aged < 64.5 years showed no significant difference (Kruskal-Wallis Test, P = .334).

Study details: Findings are from a retrospective analysis including 136 patients with RA treated with conventional synthetic DMARD or b/ts DMARD with or without methotrexate who received the third dose of SARS-CoV-2 mRNA vaccines BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna).

Disclosures: This study did not declare any specific source of funding. No conflict of interests was declared.

Source: Stahl D et al. Reduced humoral response to a third dose (booster) of SARS-CoV-2 mRNA vaccines by concomitant methotrexate therapy in elderly patients with rheumatoid arthritis. RMD Open. 2022;8(2):e002632 (Oct 10). Doi: 10.1136/rmdopen-2022-002632

Key clinical point: Concomitant methotrexate significantly reduced humoral response to the third SARS-CoV-2 mRNA vaccine in older (age ≥ 64.5 years) but not younger (age < 64.5 years) patients with rheumatoid arthritis (RA).

Major finding: Patients aged ≥ 64.5 years receiving methotrexate plus biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) vs methotrexate monotherapy or b/tsDMARD monotherapy had significantly lower serum levels of immunoglobulin G antibody for SARS-CoV-2 spike protein receptor binding domain (64.8 vs 1743.8 or 1106.0 binding antibody units/mL, respectively; Kruskal-Wallis Test, P < .001), whereas patients aged < 64.5 years showed no significant difference (Kruskal-Wallis Test, P = .334).

Study details: Findings are from a retrospective analysis including 136 patients with RA treated with conventional synthetic DMARD or b/ts DMARD with or without methotrexate who received the third dose of SARS-CoV-2 mRNA vaccines BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna).

Disclosures: This study did not declare any specific source of funding. No conflict of interests was declared.

Source: Stahl D et al. Reduced humoral response to a third dose (booster) of SARS-CoV-2 mRNA vaccines by concomitant methotrexate therapy in elderly patients with rheumatoid arthritis. RMD Open. 2022;8(2):e002632 (Oct 10). Doi: 10.1136/rmdopen-2022-002632

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk of developing all types of thyroid dysfunctions, with the risk being the highest for hypothyroidism, followed by subclinical hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism.

Major finding: Patients with RA vs non-RA control individuals were at a higher risk of developing thyroid dysfunctions such as hypothyroidism (pooled OR [pOR] 2.25; 95% CI 1.78-2.84), subclinical hypothyroidism (pOR 2.18; 95% CI 1.32-3.61), subclinical hyperthyroidism (pOR 2.13; 95% CI 1.25-3.63), and hyperthyroidism (OR 1.65; 95% CI 1.24-2.19).

Study details: Findings are from a systematic review and meta-analysis of 29 studies that evaluated thyroid dysfunction in patients with RA (n = 35,708) and non-RA control individuals (n = 149,421).

Disclosures: This study was supported by grants from the Science and Technology Bureau of Quanzhou and the Natural Science Foundation of Fujian Province. The authors declared no conflict of interests.

Source: Liu Y-j et al. Association between rheumatoid arthritis and thyroid dysfunction: A meta-analysis and systematic review. Front Endocrinol. 2022;13:1015516 (Oct 13). Doi: 10.3389/fendo.2022.1015516

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk of developing all types of thyroid dysfunctions, with the risk being the highest for hypothyroidism, followed by subclinical hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism.

Major finding: Patients with RA vs non-RA control individuals were at a higher risk of developing thyroid dysfunctions such as hypothyroidism (pooled OR [pOR] 2.25; 95% CI 1.78-2.84), subclinical hypothyroidism (pOR 2.18; 95% CI 1.32-3.61), subclinical hyperthyroidism (pOR 2.13; 95% CI 1.25-3.63), and hyperthyroidism (OR 1.65; 95% CI 1.24-2.19).

Study details: Findings are from a systematic review and meta-analysis of 29 studies that evaluated thyroid dysfunction in patients with RA (n = 35,708) and non-RA control individuals (n = 149,421).

Disclosures: This study was supported by grants from the Science and Technology Bureau of Quanzhou and the Natural Science Foundation of Fujian Province. The authors declared no conflict of interests.

Source: Liu Y-j et al. Association between rheumatoid arthritis and thyroid dysfunction: A meta-analysis and systematic review. Front Endocrinol. 2022;13:1015516 (Oct 13). Doi: 10.3389/fendo.2022.1015516

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk of developing all types of thyroid dysfunctions, with the risk being the highest for hypothyroidism, followed by subclinical hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism.

Major finding: Patients with RA vs non-RA control individuals were at a higher risk of developing thyroid dysfunctions such as hypothyroidism (pooled OR [pOR] 2.25; 95% CI 1.78-2.84), subclinical hypothyroidism (pOR 2.18; 95% CI 1.32-3.61), subclinical hyperthyroidism (pOR 2.13; 95% CI 1.25-3.63), and hyperthyroidism (OR 1.65; 95% CI 1.24-2.19).

Study details: Findings are from a systematic review and meta-analysis of 29 studies that evaluated thyroid dysfunction in patients with RA (n = 35,708) and non-RA control individuals (n = 149,421).

Disclosures: This study was supported by grants from the Science and Technology Bureau of Quanzhou and the Natural Science Foundation of Fujian Province. The authors declared no conflict of interests.

Source: Liu Y-j et al. Association between rheumatoid arthritis and thyroid dysfunction: A meta-analysis and systematic review. Front Endocrinol. 2022;13:1015516 (Oct 13). Doi: 10.3389/fendo.2022.1015516

Key clinical point: Red blood cell distribution width could serve as a useful biomarker and successfully differentiate between patients with rheumatoid arthritis (RA) and control individuals.

Major finding: Patients with RA vs. control individuals had significantly higher values for red blood cell distribution width (standardized mean difference, 0.96; P < .001); however, the mean platelet volume (P = .515) and platelet distribution width (P = .222) were not significantly different between the 2 groups.

Study details: This was a systematic review and meta-analysis of 23 studies, of which 11 studies reported data on red blood cell distribution width and included 1,221 patients with RA and 983 control individuals.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Zinellu A and Mangoni AA et al. Platelet and red blood cell volume indices in patients with rheumatoid arthritis: A systematic review and meta-analysis. Diagnostics. 2022;12(11):2633 (Oct 30). Doi: 10.3390/diagnostics12112633.

Key clinical point: Red blood cell distribution width could serve as a useful biomarker and successfully differentiate between patients with rheumatoid arthritis (RA) and control individuals.

Major finding: Patients with RA vs. control individuals had significantly higher values for red blood cell distribution width (standardized mean difference, 0.96; P < .001); however, the mean platelet volume (P = .515) and platelet distribution width (P = .222) were not significantly different between the 2 groups.

Study details: This was a systematic review and meta-analysis of 23 studies, of which 11 studies reported data on red blood cell distribution width and included 1,221 patients with RA and 983 control individuals.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Zinellu A and Mangoni AA et al. Platelet and red blood cell volume indices in patients with rheumatoid arthritis: A systematic review and meta-analysis. Diagnostics. 2022;12(11):2633 (Oct 30). Doi: 10.3390/diagnostics12112633.

Key clinical point: Red blood cell distribution width could serve as a useful biomarker and successfully differentiate between patients with rheumatoid arthritis (RA) and control individuals.

Major finding: Patients with RA vs. control individuals had significantly higher values for red blood cell distribution width (standardized mean difference, 0.96; P < .001); however, the mean platelet volume (P = .515) and platelet distribution width (P = .222) were not significantly different between the 2 groups.

Study details: This was a systematic review and meta-analysis of 23 studies, of which 11 studies reported data on red blood cell distribution width and included 1,221 patients with RA and 983 control individuals.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Zinellu A and Mangoni AA et al. Platelet and red blood cell volume indices in patients with rheumatoid arthritis: A systematic review and meta-analysis. Diagnostics. 2022;12(11):2633 (Oct 30). Doi: 10.3390/diagnostics12112633.

Key clinical point: Age is an independent contributor to seronegative rheumatoid arthritis (RA), with the effect being prominent in females but not in males.

Major finding: Rates of rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) positivity and RF/anti-CCP double positivity declined significantly with an increase in age at RA diagnosis (all P < .001). The age at disease onset was independently associated with RF (odds ratio [OR] 0.980; P < .001) and anti-CCP (OR 0.976; P < .001) positivity in patients with RA, with both the associations being significant in women (RF positivity: OR 0.979; P < .001; anti-CCP positivity: OR 0.970; P < .001) but not in men.

Study details: This was a cohort study including 1685 patients with RA (mean age at diagnosis, 51.9 years), of which 83.4% were women.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Takanashi S et al. Impacts of ageing on rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity in patients with rheumatoid arthritis. J Rheumatol. 2022 (Nov 1). Doi: 10.3899/jrheum.220526

Key clinical point: Age is an independent contributor to seronegative rheumatoid arthritis (RA), with the effect being prominent in females but not in males.

Major finding: Rates of rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) positivity and RF/anti-CCP double positivity declined significantly with an increase in age at RA diagnosis (all P < .001). The age at disease onset was independently associated with RF (odds ratio [OR] 0.980; P < .001) and anti-CCP (OR 0.976; P < .001) positivity in patients with RA, with both the associations being significant in women (RF positivity: OR 0.979; P < .001; anti-CCP positivity: OR 0.970; P < .001) but not in men.

Study details: This was a cohort study including 1685 patients with RA (mean age at diagnosis, 51.9 years), of which 83.4% were women.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Takanashi S et al. Impacts of ageing on rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity in patients with rheumatoid arthritis. J Rheumatol. 2022 (Nov 1). Doi: 10.3899/jrheum.220526

Key clinical point: Age is an independent contributor to seronegative rheumatoid arthritis (RA), with the effect being prominent in females but not in males.

Major finding: Rates of rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) positivity and RF/anti-CCP double positivity declined significantly with an increase in age at RA diagnosis (all P < .001). The age at disease onset was independently associated with RF (odds ratio [OR] 0.980; P < .001) and anti-CCP (OR 0.976; P < .001) positivity in patients with RA, with both the associations being significant in women (RF positivity: OR 0.979; P < .001; anti-CCP positivity: OR 0.970; P < .001) but not in men.

Study details: This was a cohort study including 1685 patients with RA (mean age at diagnosis, 51.9 years), of which 83.4% were women.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Takanashi S et al. Impacts of ageing on rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity in patients with rheumatoid arthritis. J Rheumatol. 2022 (Nov 1). Doi: 10.3899/jrheum.220526

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk for lung cancer compared with the general population, with seropositivity being a strong and independent risk factor above what can be explained by smoking.

Major finding: Patients with RA vs. general population were at increased risk for lung cancer (adjusted hazard ratio [aHR] 1.70; 95% CI 1.54-1.87), with the risk being even higher among ever smokers (aHR 1.82; 95% CI 1.06-3.17) or current smokers (aHR 2.73; 95% CI 1.21-6.16) and double seropositivity being a strong and independent risk factor (aHR 6.21; 95% CI 1.47-26.33).

Study details: This was a population-based matched cohort study including 44,101 patients with RA who were individually matched with 216,495 control individuals from the general population and prospectively followed for the occurrence of lung cancer.

Disclosures: This study was funded by the Swedish Research Council and other sources. K Chatzidionysiou declared receiving consulting fees from various sources. J Askling declared serving as principal investigator and having ties with various sources.

Source: Chatzidionysiou K et al. Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking. RMD Open. 2022;8(2):e002465 (Oct 21). Doi: 10.1136/rmdopen-2022-002465

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk for lung cancer compared with the general population, with seropositivity being a strong and independent risk factor above what can be explained by smoking.

Major finding: Patients with RA vs. general population were at increased risk for lung cancer (adjusted hazard ratio [aHR] 1.70; 95% CI 1.54-1.87), with the risk being even higher among ever smokers (aHR 1.82; 95% CI 1.06-3.17) or current smokers (aHR 2.73; 95% CI 1.21-6.16) and double seropositivity being a strong and independent risk factor (aHR 6.21; 95% CI 1.47-26.33).

Study details: This was a population-based matched cohort study including 44,101 patients with RA who were individually matched with 216,495 control individuals from the general population and prospectively followed for the occurrence of lung cancer.

Disclosures: This study was funded by the Swedish Research Council and other sources. K Chatzidionysiou declared receiving consulting fees from various sources. J Askling declared serving as principal investigator and having ties with various sources.

Source: Chatzidionysiou K et al. Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking. RMD Open. 2022;8(2):e002465 (Oct 21). Doi: 10.1136/rmdopen-2022-002465

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk for lung cancer compared with the general population, with seropositivity being a strong and independent risk factor above what can be explained by smoking.

Major finding: Patients with RA vs. general population were at increased risk for lung cancer (adjusted hazard ratio [aHR] 1.70; 95% CI 1.54-1.87), with the risk being even higher among ever smokers (aHR 1.82; 95% CI 1.06-3.17) or current smokers (aHR 2.73; 95% CI 1.21-6.16) and double seropositivity being a strong and independent risk factor (aHR 6.21; 95% CI 1.47-26.33).

Study details: This was a population-based matched cohort study including 44,101 patients with RA who were individually matched with 216,495 control individuals from the general population and prospectively followed for the occurrence of lung cancer.

Disclosures: This study was funded by the Swedish Research Council and other sources. K Chatzidionysiou declared receiving consulting fees from various sources. J Askling declared serving as principal investigator and having ties with various sources.

Source: Chatzidionysiou K et al. Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking. RMD Open. 2022;8(2):e002465 (Oct 21). Doi: 10.1136/rmdopen-2022-002465