A 51-year-old Japanese man was referred to us because of a 5-month history of a generalized papular eruption on the trunk and four extremities without pruritus. He consulted three dermatologic clinics and was treated individually with oral 10 mg-daily methylprednisone or clarithromycin, and additional topical corticosteroids without remarkable therapeutic effects. On examination, the patient had multiple, solid papules densely present with cobblestone-like appearance on the trunk and four limbs (Figure 1A), sparing the face, palms and soles. Individual papules were 2–3 mm in diameter and had a slightly depressed center (Figure 1B). Some papules were observed in a linear fashion, indicating Köbner phenomenon. Peripheral blood examination revealed that T-cell production of interferon-γ to tuberculosis peptides, angiotensin converting enzyme (ACE), anti-nuclear antibodies, infection tests of syphilis and hepatitis viruses, hemoglobin A1c, and serum lipids were all negative or within normal limits. Complete blood cell counts and differential leukocyte counts were normal, except for monocytosis (20.4%). The frequencies of CD3⁺, CD4⁺ and CD8⁺ cells were within normal ranges. Soluble IL-2 receptor level was slightly increased (522 U/mL; normal, ≤496). He had hypertension and was given amlodipine, which was estimated as a potential culprit drug and was discontinued upon our first examination. His family history was unremarkable.

A biopsy specimen taken from a papule on the abdomen disclosed focal or perivascular accumulation of histiocytes in the dermis and subcutaneous tissue. The histiocytes had round or oval nuclei without atypia. Multinucleated giant cells were slightly observed. There was degeneration of dermal collagen fibers lined by a palisading granulomatous reaction (Figure 1C) with Alcian-blue-positive mucin deposition (Figure 1D). No pathogen was found with Periodic acid-Schiff, Grocott, or Ziel-Neelsen staining. Immunohistochemically, the histiocytoid cells were positive for CD68 (Figure 1E), CD163, lysozyme and fascin, indicating histiocytes/macrophages, and negative for S-100 protein, CD1a and langerin, negating the possibilities of Langerhans cell histiocytosis and intermediate cell histiocytosis. We thus diagnosed the lesions as GGA. Sarcoidosis was excluded normal chest roentgenogram on annual health examination and normal serum ACE level.

We treated the patients with oral tranilast, 100 mg daily, for 4 weeks, and subsequently with narrow-band ultraviolet-B, up to 0.8 J/cm², at a 2-week interval for 8 weeks, with limited therapeutic effects. Since he was refractory to multiple treatments by the three precedent dermatologists and us, baricitinib, 2 mg daily, was initiated. Written informed consent was obtained from the patient. After 9-week treatment, the papules were markedly flattened (Figure 1F). The patient had good intervention adherence and tolerated the treatment. Currently, his eruption subsided without recurrence.

A 62-year-old Japanese woman was referred to us because of multiple lesions on the lower limbs, abdomen, and chest without pruritus. She developed an erythematous eruption on the abdomen 1 year before our examination, and then, reddish papules began to spread at the peripheries of the abdominal plaques. Subsequently, the same papular or annular lesions occurred on the chest and thighs, forming multifocal crops of papules. She was treated by a dermatologist topically with a strongest corticosteroid, which did not improve the eruption. Her family history was unremarkable. She had lipidemia. Peripheral blood examination showed that the following tests were negative or within normal limits: complete blood cell counts, differential leukocyte counts, T-cell tuberculosis test, ACE, anti-nuclear antibodies, syphilis and hepatitis virus tests, sugar level, and hemoglobin A1c. Blood chemistries disclosed high levels of total cholesterol (269 mg/dL; normal, 130–220) and LDL (181 mg/dL; normal, 70–139). Liver and renal functions were normal. On our initial examination, the patient had large erythematous patches on the abdomen with papules scattered from the peripheries (Figure 2A). Papules, measured mostly 5 mm in diameter and exhibiting depressed center were spread to the chest and thighs near the knees (Figure 2B).

Histopathologically, a papular lesion showed that histiocytes and multinucleated giant cells infiltrated in the upper to middle dermis (Figure 2C). The infiltrate was mainly present between collogen fibers, as reported in the previous study that the predominant pattern in GGA is interstitial rather than palisading [6]. In some areas, collagen fibers were slightly degenerated and alcian blue-positive material was deposited in the same foci (Figure 2F). The eruption was diagnosed as GGA. Sarcoidosis was excluded normal chest roentgenogram on annual health examination and normal serum ACE level.

Since the patient’s eruption, consisting of large patches and scattered papules, did not respond well to the strongest topical corticosteroid or 100 mg-daily tranilast, we treated her with varicitinib, 2 mg daily. Written informed consent was obtained from the patient. The patient had good intervention adherence and tolerated the treatment. Twelve weeks after the initiation, the patches and annular or popular lesions were markedly improved, leaving hyperpigmented sequelae (Figures 1D, E).