A 12-year-old female presented with rash, arthralgia, and skin ulceration for 5 years and was admitted to the First Affiliated Hospital of Henan University of Science and Technology on December 13, 2015. In 2010, she had multiple rashes and ulcers on the trunk and limbs, accompanied by exudation of a dark red liquid. She also had ulceration, peeling, and scabbing on the tongue tip and lips, affecting food intake. Her interphalangeal joints of both hands were swollen due to synovitis. At another hospital, glucocorticoid treatment was given, and the skin lesions were improved. In 2011, the rash worsened again. The fingers of both hands were swollen, with mild flexion and deformity. She tested positive for the antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA) antibody at another hospital. She received prednisone 30 mg/day and hydroxychloroquine sulfate 200 mg/day. After 1 month of treatment, most skin lesions were improved, but the lesions in the oral cavity and on hands and feet were not. She intermittently took prednisone 5-20 mg/day orally, but her parents did not take her to the hospital for medical treatment until 2015.

At admission in 2015, her medical history included the presence of a mass on the right neck since childhood that enlarged with age. It was once diagnosed with lymphadenectasis, but no treatment was given because of no discomfort. She lost a thumb tip in 2011 due to trauma. She was a first child, natural delivery, with a birth weight of 2.6 kg. Growth and development were normal. Her mother had a history of mental disorders, and the father had a mild intellectual disability. She had a younger brother, who was healthy. She had no history of genetic diseases and no familial history of such signs and symptoms. The patient was malnourished and was emaciated with a height of 110 cm and weight of 18 kg. Her skin was very thin, with old brown pigmentation over the whole body (Fig. 1A). A mass was present on the right neck, measuring about 6 × 7 cm (Fig. 1B). The superficial lymph nodes were not enlarged. Multiple ulcers and erosions were noted on the mucous membranes of tongue tip and lips, and red scabs were seen on the lips (Fig. 1C). Finger flexion and deformity were seen, and the skin on the palm was ulcerated and scabbed (Fig. 1D). The skin of bilateral plantar areas was ulcerated with bleeding and a small amount of brown secretions (Fig. 1E).

Signs and symptoms at presentation of a 12-year-old girl with systemic lupus erythematosus, Castleman disease, and paraneoplastic pemphigus. (A) Old brown pigmentation over the whole body. (B) Right neck mass. (C) Multiple ulcers and erosions on the mucous membranes of tongue tip and lips, and red scabs on the lips. (D) Finger flexion and deformity, and ulcerations and scabs of the skin on the palm. (E) Bilateral plantar areas

Blood routine examination revealed low white blood cells (3.14 × 109/L), low lymphocytes (1.4 × 109/L), low red blood cells (3.84 × 1012/L), low hemoglobin (64.2 g/L), low hematocrit (25.9%), low mean corpuscular volume (67.5 fl.), low mean corpuscular hemoglobin (19.6 pg), low platelets (71 × 109/L), high erythrocyte sedimentation rate (94 mm/h), high C-reactive protein (25.2 mg/L), albumin at 32 g/L, and high ferritin (685 ng/ml). ANA, anti-ds-DNA, anti-Ro, anti-nucleosome, and anticardiolipin antibodies were positive, while anti-CCP and anti-RF were negative. IgG was elevated (28.6/L), IgM was normal, C3 was low (0.43 g/L), and C4 was low (0.17 g/L). The bone marrow puncture was normal. The secretion culture showed no bacterial growth. Echocardiography showed tachycardia, and there was a small amount of pericardial effusion. The neck mass was solid and was considered as an enlarged lymph node. There were multiple unequal-sized hypoechoic masses, and abundant blood flow signals were seen in the peripheral region and inside. Hand X-ray showed osteoporosis of both hands, flexion of the distal part of the ring finger of the right hand, and unclear bone structure. Chest CT revealed a small amount of exudation in both lungs and small pericardial effusions. Abdominal CT showed that the spleen was slightly enlarged and revealed a stone in the vermiform appendix.

The mass was biopsied. The pathological examination revealed the classical manifestations of CD (Fig. 2A). Therefore, according to the clinical manifestations and pathological results, the primary diagnosis was SLE and CD. The mucosal skin lesions were considered as lupus vasculitis. The patient was treated with prednisone acetate 1 mg/kg/d, hydroxychloroquine sulfate 100 mg bid, leflunomide 10 mg qd, and thalidomide 25 mg qd. The skin lesions were treated with regularly changed dressing, recombinant human epidermal growth factor spray, sulfadiazine silver cream, mupirocin ointment, red light therapy, and supportive treatments.

Pathological examination of mass and heel mucosa. (A) Pathological image of mass. (B) Pathological image of heel mucosa

In October 2016, the child’s temperature was normal, the skin lesions in the palm were cured (Fig. 3A), the exudations of both feet were reduced (Fig. 3B), and the skin lesions were improved. The blood routine examination was normal. Pericardial effusion disappeared. However,after half a year of the medication treatment, the oral mucosa had not improved (Fig. 3C) until May 2017. The heel skin was used for pathological examination (Fig. 2B). The results showed hyperkeratosis, focal edema, acantholysis of the prickle cell layer, separation at the junction of epidermis and dermis, and blisters that contained red blood cells, lymphocytes, and small neutrophils. Therefore, according to the clinical manifestations and pathological examination, it was considered as PNP.

The condition of the children improved after treatments and enlarged lymph nodes in the neck. (A) Skin lesions on the palm. (B) Skin lesions under the feet. (C) The oral mucosa did not improve. (D) Specimen of the Castleman disease lesion

It was recommended to remove the tumor (Fig. 3D) and to treat with Tocilizumab (an antagonist of the Interleukin-6 receptor), but her parents refused to use Tocilizumab for treatment due to economic reasons. Therefore, patients were given surgical resection of the enlarged lymph node lesion of the neck. Symptoms associated with PNP were improved and the lump was confirmed as CD by pathological examination. The patient continued to receive oral anti-rheumatic drugs (Prednisone, Leflunomide and Hydroxychloroquine Sulfate) and was followed-up for 3 months. The patient’s limb lesions and oral ulcers have improved significantly, and they have basically healed. Currently the patient has gone to school normally. In 2019, the patient discontinued prednisone and used leflunomide intermittently, and she was not reviewed due to poor compliance. She was followed up in July 2023 with a height of 159 cm and weight of 42.4 kg, and had her first period at the age of 14. Her oral ulcer had healed (Fig. 4A), no new swollen lymph nodes were found at the neck lymph node resection site (Fig. 4B), the skin of her hands was no longer ulcerated (Fig. 4C), but there was a little skin damage on her right foot (Fig. 4D). The results of blood routine urine routine examination were normal at the time of this follow-up, and the complement was normal ,with C3 1.17 g/L and C4 2.5 g/L, while the ANA, anti-ds-DNA,, anti-nucleosome were still positive and IgG was still elevated (18.09 g/L).

The symptoms improved 6 years after operation, and there is no recurrence. (A) The oral mucosa had healed. (B) The neck did not appear any new lump. (C) Skin lesions on the palm had healed. (D) Skin lesions under the feet