January 2024 Case Study

January 2024 Case Study

Authors: Sapana Desai & Nidhi Shah

A 29-year-old Caucasian male with history of asthma and atopic dermatitis presents with a multifocal, burning, and pruritic rash that erupted three weeks ago. On physical exam, there are innumerable, erythematous, reddish-brown papules, some with central hemorrhagic crusting spread along the chest, abdomen, and upper extremities, Figure 1. Dermatopathology findings from a subsequent punch biopsy are shown in Figure 2.

Which of the following diagnosis is the patient at an increased risk of developing?

A) Dermatomyositis
B) Postherpetic Neuralgia
C) Acute Myelogenous Leukemia
D) Mucha-Habermann Disease
E) Iron Deficiency Anemia

.           

Answer: (D) Mucha-Habermann Disease

Explanation of Correct Answer:

This patient’s clinical presentation coupled with a biopsy revealing vacuolar interface dermatitis, lymphocytes in every vacuole, erythrocyte extravasation, keratinocyte necrosis, and superficial and deep perivascular lymphoid infiltrative, is indicative of pityriasis lichenoides et varioliformis acuta (PLEVA).¹

PLEVA is an idiopathic, benign, cutaneous inflammatory dermatosis with increased predilection for the trunk, proximal extremities, and flexural regions. The eruption is polymorphous, as lesions exist in all stages of development, and successive crops of lesions can last from a few weeks to months or even years before resolution.^1,2 The disease does not discriminate by race or gender and primarily affects children and young adults, with a slight male predominance. While exact etiology and pathogenesis of PLEVA remains unknown, it is speculated to be an inflammatory reaction triggered by certain infectious agents with pathogens such as Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), varicella-zoster virus (VZV), Group A Streptococcus, and herpes simplex virus type 2, an inflammatory response secondary to T-cell dyscrasia, or an immune complex-mediated hypersensitivity.² PLEVA may also develop following the use of certain medications including but not limited to atezolizumab, pembrolizumab, and topical diphenylcyclopropenone.^1,2,3

Although rare, Mucha-Habermann disease (D) may follow an existing diagnosis of PLEVA or occur de novo.^2,3 Patients affected by FUMHD present with necrotic papules that progress to plaques and large coalescent ulcers. Skin ulceration can be extensive and painful, including oral and genital mucosa. Common systemic symptoms include high fever, abdominal pain, diarrhea, central nervous system manifestations, joint pain, respiratory complications, and death.^1,2,3

Explanation of Incorrect Answers:

Dermatomyositis (A) is an inflammatory myopathy with autoimmune pathogenesis affecting women more commonly than men, with a bimodal peak of incidence between ages 5 and 14 and ages 45 and 65. Clinical presentation classically encompasses a heliotrope rash (periorbital erythema with edema, occasionally involving the cheeks and nose), Holster sign (symmetric poikiloderma of the lateral thighs below the greater trochanter), and V-sign (confluent erythematous patches over the upper central chest and lower anterior neck).^3,4  Dermatomyositis is sub-classified into adult-onset disease and juvenile disease (JDM). Serum antinuclear autoantibodies are often present, as are other myositis-specific autoantibodies, which are useful as prognostic indicators while aiding in diagnosis and management of disease. Dermatomyositis is related to and possibly results from an immune-mediated process triggered by outside factors like drugs, infectious agents, and malignancy in individuals with genetic predisposition.⁴

Postherpetic neuralgia (B) is regarded as the most common long-term complication of reactivation of the varicella-zoster virus (VZV), also known as shingles.^3,5 VZV is characterized by prodrome of pain/burning followed by the onset of a rash by 7 to 10 days. The distinctive rash presents as crops of erythematous vesicles that evolve into pustules and crusts, often in a dermatomal distribution. The hallmark clinical manifestation of postherpetic neuralgia is a lancinating/burning pain in a unilateral dermatomal pattern that persists for three or more months after the onset of a herpes zoster outbreak.⁵ Well-established risk factors for postherpetic neuralgia include age, severe immunosuppression, the presence of a prodromal phase, allodynia, ophthalmic involvement, and diabetes mellitus.^3,5 Although treatment for postherpetic neuralgia is challenging, traditional non-invasive first-line therapeutic approaches include oral and topical medications, such as gabapentin, pregabalin, tricyclic antidepressants, and lidocaine 5% patch.³

Sweet syndrome is associated with Acute Myelogenous Leukemia (C), a myeloproliferative disorder. Sweet syndrome, or acute febrile neutrophilic dermatosis, is a rare cutaneous disorder characterized by the abrupt development of painful, tender, erythematous plaques or nodules, fever greater than 38^*C, and a nodular perivascular neutrophilic dermal infiltrate without evidence of vasculitis on histologic examination.^6,7 Sweet syndrome may occur before, at the time of or after the diagnosis of malignancy. When associated with malignancy, it is more likely to be associated with older age of onset and cytopenia, and accounts for 15-20% of total cases of Sweet syndrome.⁶ While the exact pathogenesis of Sweet syndrome is elusive, genetic factors such as HLA-B54, MEFV gene mutations, and chromosome 3q abnormalities have shown to be contributory.^6,7

Iron Deficiency Anemia (E) may be associated with Blue Rubber Bleb Nevus Syndrome [BRBNS/ Bean’s Syndrome]. Patients have characteristic cutaneous findings of multiple blue to violaceous soft and compressible nodules on the skin or mucous membranes that present at birth or in early childhood and develop numerous venous malformations involving the skin and gastrointestinal tract over their’ lifetime.^8,9 Typical lesions range in size from a few millimeters to up to 4 centimeters in diameter, are rubbery in consistency, and gradually evolve with time eliciting pain most prevalent at night.⁸ Uniquely, lesions swell in gravity-dependent positions, and patients exhibit focal areas of hyperhidrosis overlying these lesions. Although most cases of BRBNS are sporadic, autosomal dominant inheritance has been suggested, as well as studies reporting stem cell factor/c-kit signaling systems contributing to vascular overgrowth. Lower gastrointestinal bleeding is the most common symptom ranging from obscure to massive bleeding leading to severe iron deficiency anemia. Other rare complications may include perforation, intussusception, intestinal torsion, disseminated intravascular coagulation, and thrombocytopenia.^8,9

References

1. Pereira, N., Brinca, A., Brites, M., Juliao, M. Tellechea, O., Goncalo, M. Pityraisis Lichenoides et Varioliformis Acuta: Case Report and Review of the Literature. Case Rep Dermatol. March 2012; 4(1): 61-65.
2. Teklehaimanot, F., Gade, A., Rubenstein, R. Pityriasis Lichenoides Et Varioliformis Acuta (PLEVA). StatPearls. 2023.
3. Bolognia, J., Schaffer, J., & Cerroni, L. (2018). Dermatology (Fourth edition.). Philadelphia,Pa: Elsevier.  of clinical medicine. Retrieved August 11, 2022, from https://pubmed.ncbi.nlm.nih.gov/32516921/
4. DeWane ME, Waldman R, Lu J. Dermatomyositis: clinical features and pathogenesis. Journal of the American Academy of Dermatology. 2020 Feb 1;82(2):267-81.
5. Gruver, C., Guthmiller, K. Postherpetic Neuralagia. 2023.
6. Guarneri, C., Wollina, U., Lotti, T., Maximov, G., Lozev, I., Gianfaldoni, S., Pidakev, I., Lotti, J., Tchernev, G. Sweet’s Syndrome (SS) in the Course of Acute Myeloid Leukemia. Open Access Maced Journal Medical Sciences. January 2018; 6(1): 105-107.
7. Vashisht, P., Goyal, A., Holmes, M. Sweet Syndrome. 2023.
8. Moghadam, A., Bagheri, M., Eslami, P., Farokhi, E., Asl, A., Khavaran, K., Iravani, S., Saeedi, S., Mehrvar, A., Dooghaie-Moghadam, M. Blue Rubber Bleb Nevus Syndrome because of 12 Years of Iron Deficiency Anemia in a Patient by Double Balloon Enteroscopy; A Case Report and Review of Literature. Middle East Journal of Digestive Diseases. 2021; 13(2): 153-159.
9. Hu, Z, Lin, X., Zhong, J., He, Qingfang., Peng, Q., Xiao, J., Chen, B., Zheng, J. Blue Rubber Bleb Nevus Syndrome with the Complication of Intussusception: A Case Report and Literature Review. Medicine (Baltimore). 2020; 99(28).