United States

Background
Scleroderma is a rare, chronic autoimmune disease that is characterized by thickening of the skin and other connective tissues in the body. Nodular scleroderma (NS) is a rare cutaneous form of scleroderma that can occur primarily with systemic sclerosis. Due to the rarity of NS, it is important to recognize these lesions, if presenting early in disease progression, as a sign of underlying scleroderma before internal organ damage becomes apparent. 

Case Presentation
A 42-year-old female with a history of systemic sclerosis presented with an enlarging left supraclavicular nodule. Upon physical exam, a 1.1cm erythematous nodule was found. The patient had clinical findings consistent with systemic sclerosis, including Raynaud’s phenomenon, gastroesophageal reflux disease, sclerodactyly, dyspnea on exertion, and skin tightening. The patient had been treated with CellCept 1500mg twice daily and responded very well to therapy. Pertinent laboratory data included speckled antinuclear antibodies (1:320 titer) and positive anti-RNA polymerase III antibodies (&gt;80 units). 

The lesion was initially excised to rule out diagnosis of a cyst. However, histopathological analysis demonstrated a nodular proliferation of dense fibrotic collagen with scattered bland fibroblasts. A sparse perivascular and periadnexal lymphocytic infiltrate in the dermis was present with notable eccrine coil trapping. A CD34 stain showed markedly diminished dermal dendritic cells within the fibrotic nodule. Considering the patient’s known history of anti-RNA polymerase III-positive systemic sclerosis and histopathological findings, the focal lesion was consistent with nodular scleroderma. No subsequent treatments were performed.

Discussion
Nodular scleroderma is an atypical cutaneous presentation of systemic sclerosis and patients who are well-controlled on immunosuppressive therapy with few to no signs of internal organ disease are still susceptible to developing these lesions. Thus, diagnosis and treatment of NS remains a challenge. NS usually presents as 2 mm - 3 cm firm nodules or plaques resembling keloid or morphea, usually distributed on the trunk, neck, proximal extremities, and face. The pathogenesis of NS is also not well understood. Previous reports have shown that there may be a role for increased expression of connective tissue growth factor, tenascin, epidermal growth factor, or transforming growth factor beta in the formation of NS. 

Furthermore, treatment of NS is difficult as these lesions are resistant to many non-surgical interventions and remain stable over time. As in our case, surgical excision of NS has been the only treatment reported so far that results in full removal of NS, but not necessarily prevention of NS recurrence.


2023 AMA Research Challenge

Systemic Sclerosis with a Rare Presentation of Nodular Scleroderma

Background
Scleroderma is a rare, chronic autoimmune disease that is characterized by thickening of the skin and other connective tissues in the body. Nodular scleroderma (NS) is a rare cutaneous form of scleroderma that can occur primarily with systemic sclerosis. Due to the rarity of NS, it is important to recognize these lesions, if presenting early in disease progression, as a sign of underlying scleroderma before internal organ damage becomes apparent. 

Case Presentation
A 42-year-old female with a history of systemic sclerosis presented with an enlarging left supraclavicular nodule. Upon physical exam, a 1.1cm erythematous nodule was found. The patient had clinical findings consistent with systemic sclerosis, including Raynaud’s phenomenon, gastroesophageal reflux disease, sclerodactyly, dyspnea on exertion, and skin tightening. The patient had been treated with CellCept 1500mg twice daily and responded very well to therapy. Pertinent laboratory data included speckled antinuclear antibodies (1:320 titer) and positive anti-RNA polymerase III antibodies (>80 units). 

The lesion was initially excised to rule out diagnosis of a cyst. However, histopathological analysis demonstrated a nodular proliferation of dense fibrotic collagen with scattered bland fibroblasts. A sparse perivascular and periadnexal lymphocytic infiltrate in the dermis was present with notable eccrine coil trapping. A CD34 stain showed markedly diminished dermal dendritic cells within the fibrotic nodule. Considering the patient’s known history of anti-RNA polymerase III-positive systemic sclerosis and histopathological findings, the focal lesion was consistent with nodular scleroderma. No subsequent treatments were performed.

Discussion
Nodular scleroderma is an atypical cutaneous presentation of systemic sclerosis and patients who are well-controlled on immunosuppressive therapy with few to no signs of internal organ disease are still susceptible to developing these lesions. Thus, diagnosis and treatment of NS remains a challenge. NS usually presents as 2 mm - 3 cm firm nodules or plaques resembling keloid or morphea, usually distributed on the trunk, neck, proximal extremities, and face. The pathogenesis of NS is also not well understood. Previous reports have shown that there may be a role for increased expression of connective tissue growth factor, tenascin, epidermal growth factor, or transforming growth factor beta in the formation of NS. 

Furthermore, treatment of NS is difficult as these lesions are resistant to many non-surgical interventions and remain stable over time. As in our case, surgical excision of NS has been the only treatment reported so far that results in full removal of NS, but not necessarily prevention of NS recurrence.


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Lymphomatoid papulosis (LyP) is a chronic cutaneous CD30-positive lymphoproliferative disorder that is characterized by red-to-violaceous crops of papulonodular skin lesions. Although LyP carries a positive prognosis, there is consensus that LyP is associated with a history of or subsequent development of lymphoma. Herein, we present a case of LyP in a patient with a history of cutaneous B-cell lymphoma. The patient is a 67-year-old male with a history of treated cutaneous B-cell lymphoma two years prior to presentation, currently in remission, presenting with a two week history of painful hemorrhagic papules on his hands. Biopsy revealed a dense lymphomatoid infiltrate with admixed histiocytes and dermal hemorrhage. Tumor cells expressed CD3 and CD4, with marked loss of CD7. Small clusters of CD30+ cells were noted. There was no significant expression of CD20, CD56, or myeloperoxidase. At subsequent follow up, his original lesions were healing, but he had developed a new crop of lesions on the foot and both hands. Given the patient’s clinical course and histopathologic findings, a diagnosis of LyP subtype C was favored. The patient’s presentation was notable due to antecedent history of cutaneous B cell lymphoma, in addition to confinement to acral sites.

Lymphomatoid Papulosis Type C in Patient with History of Cutaneous B-Cell Lymphoma

Background
Drug-induced hypersensitivity syndrome (DIHS) is a severe, potentially life-threatening drug reaction with cutaneous and internal organ involvement. DIHS can lead to various autoimmune conditions, occurring in about 10% of patients, including thyroiditis. This case highlights the need for post-DIHS thyroiditis screening.

Case Presentation
A 32-year-old woman presented to the emergency department with fever, morbilliform eruption, facial swelling, lymphadenopathy, and laboratory studies notable for atypical lymphocytes (4%), eosinophilia (1400), and aminotransferase abnormalities (AST 61, ALT 265). Two weeks prior, she initiated a course of oral trimethoprim-sulfamethoxazole. History, clinical exam, and laboratory findings were consistent with DIHS. She was treated with high-dose corticosteroids with a resolution of the eruption and stabilization of hepatic enzymes. At follow-up in an outpatient dermatology clinic four weeks after discharge, she was noted to have clinically painful thyromegaly, fever, tachycardia, and palpitations. She was referred to the ED to expedite workup for suspected symptomatic hyperthyroidism. Workup revealed TSH of 0.01 (L), FT4 >7.7 (H), TSI <0.10, TRAb negative, and TPO Ab 202 (H). Thyroid ultrasound showed enlarged thyroid with heterogenous echotexture. Endocrinology diagnosed her with thyroiditis and prescribed atenolol for symptom management. She continued to have heat intolerance, palpitations, and faint pink macules on her lower legs. She initiated low-dose methimazole with a resolution of symptoms.

Discussion

One of the most common drug classes to cause post-DIHS autoimmune thyroiditis are sulfa drugs and antiepileptics. The most commonly seen issues that arise in the thyroid post-DIHS are Hashimoto’s thyroiditis and Graves’ disease, which have been observed to occur between 2 months and 3 years after the diagnosis of DIHS. As seen in this case, the patient experienced debilitating symptoms of thyroiditis within 1 month, which could have been minimized with early screening and recognition. This case emphasizes the importance of dermatologic follow-up for patients diagnosed with DIHS and the role of post-DIHS screening for autoimmune thyroid disease, as missed diagnosis of delayed sequelae can lead to significant morbidity.

Importance of Post-Drug Induced Hypersensitivity Syndrome Thyroiditis Screening

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Aching Adipose: Shedding Light on Dercum’s Disease

Lip and face lesions are recognized in dermatology as significantly distressing for patients. There are stereotypes associated with different lesions in this area that affect patients deeply, motivating them to seek care immediately. The average population or clinician is aware of common lip lesions, the most diagnosed of which is herpes simplex virus. Dermatologists must continue to be aware of unique lip and face lesions as they may grow rapidly, be worrisome, and affect the patient’s perception of themselves and psychological well-being. We present the case of neutrophilic sebaceous adenitis, which is an incredibly rare condition that has been reported minimally in the literature. Recognition of rapidly growing lesions, like our patients, is vital for proper diagnosis and treatment.
A 74-year-old female presented to the dermatology clinic with a 5-day history of a rapidly progressive lower lip lesion. Valacyclovir and Carmex only minimally improved her condition. Examination was significant for tenderness to palpation. The patient had no other lesions, no preceding trauma or bites, and no systemic symptoms. Histopathology showed a somewhat dense, superficial and deep, perivascular and periadnexal infiltrate composed predominantly of lymphocytes. The overlying epidermis showed some interface changes with a few necrotic keratinocytes as well as a focal but prominent neutrophilic infiltrate involving a sebaceous gland lobule. No increased dermal mucin was identified on Alcian blue stain. The patient discontinued valacyclovir and treated the lesion with triamcinolone 0.1% twice a day for a few weeks until it cleared. 
Neutrophilic sebaceous adenitis is a very rare condition. Pathogenesis is unknown but triggers such as sun exposure, antibiotics, and febrile illness have been reported. Lesions can progress over days to months and are typically asymptomatic. Recognition of this lesion around the lips and face is imperative as a differential diagnosis for providers to be aware of. Histopathology typically shows an inflammatory infiltrate, particularly of neutrophils and lymphocytes, around sebaceous glands. Sebocytes may be necrosed and further inflammatory infiltrates may be noted around the dermis. There are no current dermatologic guidelines on management although case reports have shown successful treatment with topical or oral steroids, metronidazole, or isotretinoin.

Looking Beyond the Ordinary Lip Lesion: A Rapidly Progressive Case of Neutrophilic Sebaceous Adenitis

Dermatofibromas are benign cutaneous soft-tissue tumors characterized by solitary or multiple, firm red-brown to black dermal nodules found on the trunk or extremities. Dermatofibromas most frequently affect middle-aged adults and have a slight preponderance in females. Variants of dermatofibroma include hemosiderotic, aneurysmal, epithelioid and deep fibrous histiocytomas, cellular, lipidized, lichenoid, keloidal, atrophic, and atypical. 

Diagnosis of the classical type of dermatofibroma is made clinically and based on dermoscopic patterns; however, the clinical and histologic heterogeneity observed in dermatofibroma variants can pose a diagnostic challenge and may be difficult to distinguish from potentially aggressive malignancies. Notably, hemosiderotic dermatofibroma has been reported to clinically simulate melanoma, while atypical dermatofibroma, is often mistaken histologically for sarcoma. 

Herein, we report a unique presentation of a patient with a recurrent atypical melanocytic nevus and multiple benign dermatofibromas masquerading as potentially malignant counterparts.

Dermatological Deception: Massive Dermatofibroma and Atypical Melanocytic Nevus Mimicking Malignancy

Background 
Lactation support in transgender women is increasingly recognized as clinically important yet has limited clinical precedent. While previous case reports describe successful lactation induction their protocols involve domperidone, a galactagogue unavailable for this purpose in the US and recommended against by the US Food and Drug Administration (FDA). We present a case of successful lactation induction in a transgender woman using a protocol not involving galactagogues. 
Case Presentation 
Our patient was a 36-year-old transgender woman, a United States military veteran 
receiving care through the Veterans Health Administration (VHA), who was planning on having a child with her partner and wanted to breastfeed. Her partner, a transgender man, carried and delivered the child and wished to return to testosterone use shortly after delivery. Her primary goals included sufficient milk production to allow bonding, even if not the sole source of infant nutrition. Our multidisciplinary team included a clinical pharmacist with gender-affirming hormone therapy expertise and a lactation specialist with gender-affirming therapy expertise. Our patient was status post orchiectomy with an initial testosterone level of 27 ng/dL, and on a dose of 4mg PO 17-beta estradiol. We began the patient’s lactation induction 98 days prior to her partner’s pregnancy and 377 days prior to her 
partner’s eventual due date. Our protocol involved 1) increased estrogen and 
progesterone to mimic physiologic levels during pregnancy; 2) physical nipple stimulation using a breast pump; and 3) reduced estrogen and progesterone shortly before delivery to mimic physiologic levels after birth. We opted against a galactagogue due to FDA recommendations against domperidone as well as patient concerns of side effects with other galactagogues. Interestingly, our patient’s estradiol levels remained under 200 pg/mL throughout the lactation induction process, even at higher levels of 17-beta estradiol dosing. This is in consonance with other published case-reports on lactation-induction in transwomen. 
Discussion 
Working with a multidisciplinary team including pharmacy and lactation specialists and using a protocol involving (1) initial increase of estradiol and progesterone, (2) nipple stimulation, and (3) eventual reduction of estradiol and progesterone, our patient was able to lactate without the use of galactagogues, allowing her to meet her goal of bonding with her baby. This is the first reported case of successful lactation induction without galactagogues for a transgender woman to our knowledge, and provides an example protocol modeled on physiologic lactation stimuli that other clinicians may adapt with their own patients in similar circumstances.

Inducing lactation in a transgender woman without galactagogues: A case report

Acute osteomyelitis in the setting of chronic steroid therapy for the treatment of 17-alpha-hydroxylase deficient congenital adrenal hyperplasia

The association between viral illness, inflammation, and organ dysfunction and damage is well-established throughout the literature. The interaction between angiotensin-converting enzyme 2 (ACE2) receptors and SARS-CoV-2 has been associated with the pathogenesis of SARS-CoV-2-related illness. COVID-19 can result in gastrointestinal complications due to direct or indirect insult (cytokine storm). Diarrhea is a common gastrointestinal manifestation of pancreatic insufficiency, inflammatory bowel disease, and SARS-CoV-2 infection. In COVID-19 patients, it’s the most common GI manifestation. We describe a unique case of COVID-19-induced concurrent exocrine Pancreatic Insufficiency and Inflammatory Bowel Disease that presented as chronic diarrhea. Given that the long-term effects of COVID-19 remain unknown, this case underscores the importance of systematically documenting COVID-19 manifestations to establish a temporal pattern of post-infection pathology for future research.

Long COVID: A Case of Concomitant Pancreatic Insufficiency with Inflammatory Bowel Disease

Background
This case report describes a rare extragonadal germ cell tumor, primary yolk sac tumor (YST) of the liver, which should be included in the differential of a young adult presenting with painless jaundice. There have been approximately 20 reported cases, the first being in 1975, of which only 5 are adult males. The estimated mortality rate for patients diagnosed with YST of the liver is greater than 50%.
Case Presentation
A 32-year-old male was referred from an outside facility for evaluation of painless jaundice. He had multiple prior hospitalizations which revealed a recurring distal common bile duct (CBD) stricture despite multiple biliary stent placements. A computed tomography (CT) scan was obtained and redemonstrated the distal CBD stricture. An endoscopic ultrasound (EUS) was then performed, showing enlarged peri-portal and peri-ductal lymph nodes in addition to a dilated CBD secondary to a distal stricture. A fine need biopsy (FNB) was obtained from the largest peri-ductal lymph node. An endoscopic retrograde cholangiopancreatography (ERCP) was then performed with placement of a plastic biliary stent to decompress the biliary tree and relieve the CBD obstruction secondary to lymphadenopathy. His serum bilirubin levels normalized 1 week later. FNB staining was consistent with YST. Subsequently, a testicular ultrasound was performed, but showed no evidence of a primary testicular mass, which confirmed the diagnosis of a primary YST of the liver. The patient was referred to oncology where he started a curative-intent chemotherapy regimen of bleomycin, etoposide, and cisplatin.
Discussion
There are three existing hypotheses for YST of the liver pathogenesis: aberrant migration of primordial germ cells, reverse migration of the transformed germ cells from the testes, and abnormal differentiation of somatic cells. FNB stained positive for cytokeratin 7, alpha fetoprotein, and glypican-3, which suggested either adenocarcinoma or YST. A positive sal-like protein 4 stain confirmed the presence of YST. Given this similar staining pattern between adenocarcinoma and YST, it is important to consider YST in the differential diagnosis, especially in young patients presenting with jaundice. Primarily because its management is very different often needing only chemotherapy and not a Whipple procedure which is usually seen with adenocarcinoma.


Yolk Sac Tumor of the Liver: A Rare Cause of Bile Duct Obstruction

Eosinophilic gastroenteritis is an underdiagnosed condition that presents with long term complications in patients with vague gastrointestinal symptoms. The case of a 72-year-old man highlights the common symptoms of eosinophilic gastroenteritis (abdominal pain, dysphagia, diarrhea) and how severe complications can arise such as cholecystitis prompting surgery. We illustrate the importance of identifying features of eosinophilic gastroenteritis and limiting misdiagnosis, such as IBS. This allows access to appropriate treatment before severe complication arise. Family physicians play and key role in diagnosis and management of this condition. Our patient spent 3 weeks on the inpatient service, went through many imaging and laboratory tests, and eventually underwent a prompt cholecystectomy for a gallbladder perforation secondary to acute necrotizing cholecystitis. Likely, if diagnosed earlier, this patient may have been able to avoid this complication that led to surgery by receiving proper treatment. The case review highlights the clinical features, pathophysiology, diagnostic criteria, and current guidelines for treatment of eosinophilic gastroenteritis.

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Systemic Sclerosis with a Rare Presentation of Nodular Scleroderma

Next from 2023 AMA Research Challenge

Lymphomatoid Papulosis Type C in Patient with History of Cutaneous B-Cell Lymphoma